Nuestros investigadores

Gema Fruhbeck Martínez

Publicaciones científicas más recientes (desde 2010)

Autores: Frühbeck, Gema; Escalada, J, (Autor de correspondencia)
Revista: NUTRIENTS
ISSN 2072-6643  Vol. 11  Nº 3  2019  págs. 677
Non-alcoholic fatty liver disease (NAFLD) is a major global health threat due to its growing incidence and prevalence. It is becoming the leading cause of liver disease in addition to its strong association with cardio-metabolic disease. Therefore, its prevention and treatment are of strong public interest. Therapeutic approaches emphasize lifestyle modifications including physical activity and the adoption of healthy eating habits that intend to mainly control body weight and cardio-metabolic risk factors associated with the metabolic syndrome. Lifestyle interventions may be reinforced by pharmacological treatment in advanced stages, though there is still no registered drug for the specific treatment of NAFLD. The purpose of this review is to assess the evidence available regarding the impact of dietary recommendations against NAFLD, highlighting the effect of macronutrient diet composition and dietary patterns in the management of NAFLD.
Autores: Becerril, Sara; Rodríguez, Amaia; Catalán, V; et al.
Revista: NUTRIENTS
ISSN 2072-6643  Vol. 11  Nº 9  2019  págs. 2129
Leptin, the product of the ob gene, was originally described as a satiety factor, playing a crucial role in the control of body weight. Nevertheless, the wide distribution of leptin receptors in peripheral tissues supports that leptin exerts pleiotropic biological effects, consisting of the modulation of numerous processes including thermogenesis, reproduction, angiogenesis, hematopoiesis, osteogenesis, neuroendocrine, and immune functions as well as arterial pressure control. Nitric oxide (NO) is a free radical synthesized from L-arginine by the action of the NO synthase (NOS) enzyme. Three NOS isoforms have been identified: the neuronal NOS (nNOS) and endothelial NOS (eNOS) constitutive isoforms, and the inducible NOS (iNOS). NO mediates multiple biological effects in a variety of physiological systems such as energy balance, blood pressure, reproduction, immune response, or reproduction. Leptin and NO on their own participate in multiple common physiological processes, with a functional relationship between both factors having been identified. The present review describes the functional relationship between leptin and NO in different physiological processes.
Autores: Gargallo, Javier; et al.
Revista: EXPERT OPINION ON PHARMACOTHERAPY
ISSN 1465-6566  Vol. 20  Nº 4  2019  págs. 367 - 371
Autores: Anon-Hidalgo, J.; Catalán, V; Rodríguez, Amaia; et al.
Revista: AGING-US
ISSN 1945-4589  Vol. 11  Nº 6  2019  págs. 1733 - 1744
Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor beta (TGF beta) superfamily which declines with age and exerts anti-aging regenerative effects in skeletal muscle in mice. However, recent data in humans and mice are conflicting casting doubts about its true functional actions. The aim of the present study was to compare the circulating concentrations of GDF11 in individuals of different ages as well as body weight and glycemic status. Serum concentrations of GDF11 were measured by ELISA in 319 subjects. There was a significant increase in GDF11 concentrations in people in the 41-50 y group and a decline in the elder groups (61-70 and 71-80 y groups, P=0.008 for the comparison between all age groups). However, no significant correlation between fat-free mass index (FFMI), a formula used to estimate the amount of muscle mass in relation to height, and IogGDF11 was observed (r=0.08, P=0.197). Moreover, no significant differences in circulating concentrations of GDF11 regarding obesity or glycemic status were found. Serum GDF11 concentrations in humans decrease in older ages being unaltered in obesity and T2D. Further studies should determine the exact pathophysiological role of GDF11 in aging.
Autores: Ortega, F. J., (Autor de correspondencia); Moreno-Navarrete, J. M.; Mercader, J. M.; et al.
Revista: FASEB JOURNAL
ISSN 0892-6638  Vol. 33  Nº 8  2019  págs. 9656 - 9671
During adipogenesis, preadipocytes' cytoskeleton reorganizes in parallel with lipid accumulation. Failure to do so may impact the ability of adipose tissue (AT) to shift between lipid storage and mobilization. Here, we identify cytoskeletal transgelin 2 (TAGLN2) as a protein expressed in AT and associated with obesity and inflammation, being normalized upon weight loss. TAGLN2 was primarily found in the adipose stromovascular cell fraction, but inflammation, TGF-beta, and estradiol also prompted increased expression in human adipocytes. Tagln2 knockdown revealed a key functional role, being required for proliferation and differentiation of fat cells, whereas transgenic mice overexpressing Tagln2 using the adipocyte protein 2 promoter disclosed remarkable sex-dependent variations, in which females displayed healthy obesity and hypertrophied adipocytes but preserved insulin sensitivity, and males exhibited physiologic changes suggestive of defective AT expandability, including increased number of small adipocytes, activation of immune cells, mitochondrial dysfunction, and impaired metabolism together with decreased insulin sensitivity. The metabolic relevance and sexual dimorphism of TAGLN2 was also outlined by genetic variants that may modulate its expression and are associated with obesity and the risk of ischemic heart disease in men. Collectively, current findings highlight the contribution of cytoskeletal TAGLN2 to the obese phenotype in a gender-dependent manner.-Ortega, F. J., Moreno-Navarrete, J. M., Mercader, J. M., Gomez-Serrano, M., Garcia-Santos, E., Latorre, J., Lluch, A., Sabater, M., Caballano-Infantes, E., Guzman, R., Macias-Gonzalez, M., Buxo, M., Girones, J., Vilallonga, R., Naon, D., Botas, P., Delgado, E., Corella, D., Burcelin, R., Fruhbeck, G., Ricart, W., Simo, R., Castrillon-Rodriguez, I., Tinahones, F. J., Bosch, F., Vidal-Puig, A., Malagon, M. M., Peral, B., Zorzano, A., Fernandez-Real, J. M. Cytoskeletal transgelin 2 contributes to gender-dependent adipose tissue expandability and immune function.
Autores: Christou, G. A. ; Katsiki, N.; Blundell, J. ; et al.
Revista: OBESITY REVIEWS
ISSN 1467-7881  Vol. 20  Nº 6  2019  págs. 805 - 815
Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with a long elimination half-life, allowing subcutaneous (sc) administration once per week. Both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) recently approved once-weekly sc semaglutide for the treatment of type 2 diabetes mellitus (T2DM). The weight loss efficacy of once-weekly sc semaglutide appears to be superior compared with the other once-weekly GLP-1 RAs in patients with T2DM. Semaglutide was recently evaluated as an antiobesity drug in a phase II dose-finding trial, which demonstrated superior weight loss efficacy of once daily sc semaglutide compared with both placebo and once daily 3.0 mg liraglutide in patients with obesity but without T2DM. The magnitude of semaglutide-induced weight loss in this study exceeded the criteria of both the EMA and FDA for antiobesity drugs, and there were no safety concerns, indicating the eligibility of once daily sc semaglutide as a future antiobesity drug.
Autores: Anon-Hidalgo, J.; Catalán, V; Rodríguez, Amaia; et al.
Revista: JOURNAL OF CLINICAL MEDICINE
ISSN 2077-0383  Vol. 8  Nº 6  2019  págs. 878
Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor (TGF)-beta superfamily which declines with age and has been proposed as an anti-aging factor with regenerative effects in skeletal muscle in mice. However, recent data in humans and mice are conflicting, casting doubts about its true functional actions. The aim of the present study was to analyze the potential involvement of GFD11 in energy homeostasis in particular in relation with thyroid hormones. Serum concentrations of GDF11 were measured by enzyme-linked immunosorbent assay (ELISA) in 287 subjects. A highly significant positive correlation was found between GDF11 and thyroid-stimulating hormone (TSH) concentrations (r = 0.40, p < 0.001). Neither resting energy expenditure (REE) nor REE per unit of fat-free mass (REE/FFM) were significantly correlated (p > 0.05 for both) with GDF11 levels. In a multiple linear regression analysis, the model that best predicted logGDF11 included logTSH, leptin, body mass index (BMI), age, and C-reactive protein (logCRP). This model explained 37% of the total variability of logGDF11 concentrations (p < 0.001), with only logTSH being a significant predictor of logGDF11. After segregating subjects by TSH levels, those within the low TSH group exhibited significantly decreased (p < 0.05) GDF11 concentrations as compared to the normal TSH group or the high TSH group. A significant correlation of GDF11 levels with logCRP (r = 0.19, p = 0.025) was found. GDF11 levels were not related to the presence of hypertension or cardiopathy. In conclusion, our results show that circulating concentrations of GDF11 are closely associated with TSH concentrations and reduced in subjects with low TSH levels. However, GDF11 is not related to the regulation of energy expenditure. Our data also suggest that GDF11 may be involved in the regulation of inflammation, without relation to cardiac function. Further research is needed to elucidate the role of GDF11 in metabolism and its potential involvement in thyroid pathophysiology.
Autores: Pérez-Pevida, Belén, (Autor de correspondencia); Núñez, Jorge María; Romero, S.; et al.
Revista: JOURNAL OF TRANSLATIONAL MEDICINE
ISSN 1479-5876  Vol. 17  2019  págs. 48
Background and aims: Obesity is associated with impaired glucose tolerance which is a risk factor for cardiovascular risk. However, the oral glucose tolerance test (OGTT) is not usually performed in patients with normal fasting glycaemia, thus offering false reassurance to patients with overweight or obesity who may have post-prandial hyperglycaemia. As an alternative to resource demanding OGTTs, we aimed to examine the predictive value of anthropometric measures of total and central fat distribution for post-prandial hyperglycaemia in patients with overweight and obesity with normal fasting glycaemia enrolled in the DICAMANO study. Methods: We studied 447 subjects with overweight/obesity with a fasting glucose value <= 5.5 mmol l(-1) (99 mg dl(-1)) and BMI >= 25 kg/m(2) who underwent a 75-g OGTT. Post-prandial hyperglycaemia was defined as a glucose level >= 7.8 mmol l(-1) (140 mg dl(-1)) 2-h after the OGTT. The anthropometric measurements included body mass index, body adiposity index, waist circumference, neck circumference, waist-to-hip ratio and waist-to-height ratio. Results: The prevalence of post-prandial hyperglycaemia was 26%. Mean 1-h OGTT glucose levels, insulin resistance and beta cell dysfunction was higher in those subjects in the highest tertile for each anthropometric measurement, irrespective of fasting glucose level. Central fat depot anthropometric measurements were strongly and independently associated with an increased risk of post-prandial hyperglycaemia. After multivariable-adjustment for fasting plasma glucose level, smoking, and physical activity level, the odds ratio (95% confidence intervals) for the presence of post-prandial hyperglycaemia for neck circumference, waist circumference and waist-to-height ratio were 3.3 (1.4, 7.7), 2.4 (1.4, 4.4) and 2.5 (1.4, 4.5), respectively. Conclusions: In this large and comprehensively phenotyped cohort, one in four subjects had post-prandial hyperglycaemia despite normal fasting glycaemia. Anthropometric indices of central fat distribution were strongly and independently associated with an increased risk of post-prandial hyperglycaemia. These results support the association between central adiposity and glucose derangements and demonstrate the clinical usefulness of anthropometric measurements as screening tools for the selection of patients who are most likely to benefit from an OGTT.
Autores: Frühbeck, Gema, (Autor de correspondencia); Busetto, L.; Dicker, D. ; et al.
Revista: OBESITY FACTS
ISSN 1662-4025  Vol. 12  Nº 2  2019  págs. 131 - 136
Obesity is a frequent, serious, complex, relapsing, and chronic disease process that represents a major public health problem. The coining of obesity as an adiposity-based chronic disease (ABCD) is of particular relevance being in line with EASO's proposal to improve the International Classification of Diseases ICD-11 diagnostic criteria for obesity based on three dimensions, namely etiology, degree of adiposity, and health risks. The body mass index as a unique measurement of obesity does not reflect the whole complexity of the disease. Obesity complications are mainly determined by 2 pathological processes, i.e., physical forces (fat mass disease) as well as endocrine and immune responses (sick fat disease), which are embedded in a cultural and physical context leading to a specific ABCD stage. (c) 2019 The Author(s) Published by S. Karger AG, Basel
Autores: Ezquerro, S.; Mocha, F.; Frühbeck, Gema; et al.
Revista: JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN 0021-972X  Vol. 104  Nº 1  2019  págs. 21 - 37
CONTEXT: Human obesity is associated with increased circulating TNF-¿, a proinflammatory cytokine that induces hepatocyte cell death. OBJECTIVE: The potential beneficial effects of acylated and desacyl ghrelin in the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis in obesity via the inhibition of TNF-¿-induced hepatocyte apoptosis, autophagic cell death, and pyroptosis were investigated. DESIGN, SETTINGS, AND PARTICIPANTS: Plasma ghrelin isoforms and TNF-¿ were measured in 158 participants, and hepatocyte cell death was evaluated in liver biopsies from 76 patients with morbid obesity undergoing bariatric surgery with available liver echography and pathology analysis. The effect of acylated and desacyl ghrelin on basal and TNF-¿-induced cell death was determined in vitro in human HepG2 hepatocytes. RESULTS: Circulating TNF-¿ and the acylated/desacyl ghrelin ratio were increased, whereas desacyl ghrelin levels were decreased in patients with obesity and NAFLD. Six months after bariatric surgery, decreased acylated/desacyl ghrelin levels, and improved hepatic function were found. Patients with obesity and type 2 diabetes showed increased hepatic ghrelin O-acyltransferase transcripts as well as an increased hepatic apoptosis, pyroptosis, and compromised autophagy. In HepG2 hepatocytes, acylated and desacyl ghrelin treatment reduced TNF-¿-induced apoptosis, evidenced by lower caspase-8 and caspase-3 cleavage, as well as TUNEL-positive cells and pyroptosis, revealed by decreased caspase-1 activation and lower high-mobility group box 1 expression. Moreover, acylated ghrelin suppressed TNF-¿-activated hepatocyte autophagy, as evidenced by a decreased LC3B-II/I ratio and increased p62 accumulation via AMPK/mTOR. CONCLUSIONS: Ghrelin constitutes a protective factor against hepatocyte cell death. The increased acylated/desacyl ghrelin ratio in patients with obesity and NAFLD might constitute a compensatory mechanism to overcome TNF-¿-induced hepatocyte apoptosis, autophagy, and pyroptosis.
Autores: Grattagliano, I. ; Montezinho, L. P.; Oliveira, P. J.; et al.
Revista: BIOCHEMICAL PHARMACOLOGY
ISSN 0006-2952  Vol. 160  2019  págs. 34 - 45
Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by the excessive accumulation of triglycerides in hepatocytes. NAFLD is the most frequent chronic liver disease in developed countries, and is often associated with metabolic disorders such as obesity and type 2 diabetes. NAFLD definition encompasses a spectrum of chronic liver abnormalities, ranging from simple steatosis (NAFL), to steatohepatitis (NASH), significant liver fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD, therefore, represents a global public health issue. Mitochondrial dysfunction occurs in NAFLD, and contributes to the progression to the necro-inflammatory and fibrotic form (NASH). Disrupted mitochondrial function is associated with a decrease in the energy levels and impaired redox balance, and negatively affects cell survival by altering overall metabolism and subcellular trafficking. Such events reduce the tolerance of hepatocytes towards damaging hits, and favour the injurious effects of extra-cellular factors. Here, we discuss the role of mitochondria in NAFLD and focus on potential therapeutic approaches aimed at preserving mitochondrial function.
Autores: Izaguirre, Maitane; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: JOURNAL OF CLINICAL MEDICINE
ISSN 2077-0383  Vol. 8  Nº 4  2019  págs. 479
Objective: Glucagon-like peptide (GLP)-1 has been proposed as a key candidate in glucose improvements after bariatric surgery. Our aim was to explore the role of GLP-1 in surgically-induced type 2 diabetes (T2D) improvement and its capacity to regulate human adipocyte inflammation. Methods: Basal circulating concentrations of GLP-1 as well as during an oral glucose tolerance test (OGTT) were measured in lean and obese volunteers with and without T2D (n = 93). In addition, GLP-1 levels were determined before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 77). The impact of GLP-1 on inflammation signalling pathways was also evaluated. Results: We show that the reduced (p < 0.05) circulating levels of GLP-1 in obese T2D patients increased (p < 0.05) after RYGB. The area under the curve was significantly lower in obese patients with (p < 0.01) and without (p < 0.05) T2D compared to lean volunteers while obese patients with T2D exhibited decreased GLP-1 levels at baseline (p < 0.05) and 120 min (p < 0.01) after the OGTT. Importantly, higher (p < 0.05) pre-operative GLP-1 concentrations were found in patients with T2D remission after RYGB. We also revealed that exendin-4, a GLP-1 agonist, downregulated the expression of inflammation-related genes (IL1B, IL6, IL8, TNF) and, conversely, upregulated the mRNA levels of ADIPOQ in human visceral adipocytes. Furthermore, exendin-4 blocked (p < 0.05) LPS-induced inflammation in human adipocytes via downregulating the expression and secretion of key inflammatory markers. Conclusions: Our data indicate that GLP-1 may contribute to glycemic control and exert a role in T2D remission after RYGB. GLP-1 is also involved in limiting inflammation in human visceral adipocytes.
Autores: Becerril, Sara, (Autor de correspondencia); Rodríguez, Amaia; Catalán, V; et al.
Revista: GENES
ISSN 2073-4425  Vol. 10  Nº 3  2019  págs. 184
The role of extracellular matrix (ECM) remodeling in fibrosis progression in nonalcoholic fatty liver disease (NAFLD) is complex and dynamic, involving the synthesis and degradation of different ECM components, including tenascin C (TNC). The aim was to analyze the influence of inducible nitric oxide synthase (iNOS) deletion on inflammation and ECM remodeling in the liver of ob/ob mice, since a functional relationship between leptin and iNOS has been described. The expression of molecules involved in inflammation and ECM remodeling was analyzed in the liver of double knockout (DBKO) mice simultaneously lacking the ob and the iNOS genes. Moreover, the effect of leptin was studied in the livers of ob/ob mice and compared to wild-type rodents. Liver inflammation and fibrosis were increased in leptin-deficient mice. As expected, leptin treatment reverted the obesity phenotype. iNOS deletion in ob/ob mice improved insulin sensitivity, inflammation, and fibrogenesis, as evidenced by lower macrophage infiltration and collagen deposition as well as downregulation of the proinflammatory and profibrogenic genes including Tnc. Circulating TNC levels were also decreased. Furthermore, leptin upregulated TNC expression and release via NO-dependent mechanisms in AML12 hepatic cells. iNOS deficiency in ob/ob mice improved liver inflammation and ECM remodeling-related genes, decreasing fibrosis, and metabolic dysfunction. The activation of iNOS by leptin is necessary for the synthesis and secretion of TNC in hepatocytes, suggesting an important role of this alarmin in the development of NAFLD.
Autores: Steward, T. ; Mestre-Bach, G.; Granero, R. ; et al.
Revista: SCIENTIFIC REPORTS
ISSN 2045-2322  Vol. 9  Nº 1  2019  págs. 7910
Orexins/hypocretins are neuropeptides implicated in numerous processes, including food intake and cognition. The role of these peptides in the psychopathology of anorexia nervosa (AN) remains poorly understood. The aim of the current study was to evaluate the associations between plasma orexin-A (OXA) concentrations and neuropsychological functioning in adult women with AN, and a matched control group. Fasting plasma OXA concentrations were taken in 51 females with AN and in 51 matched healthy controls. Set-shifting was assessed using the Wisconsin Card Sorting Test (WCST), whereas decision making was measured using the Iowa Gambling Task (IGT). The AN group exhibited lower plasma OXA levels than the HC group. Lower mean scores were obtained on the IGT in AN patients. WCST perseverative errors were significantly higher in the AN group compared to HC. In both the AN and HC group, OXA levels were negatively correlated with WCST non-perseverative errors. Reduced plasma OXA concentrations were found to be associated with set-shifting impairments in AN. Taking into consideration the function of orexins in promoting arousal and cognitive flexibility, future studies should explore whether orexin partly underpins the cognitive impairments found in AN.
Autores: Frühbeck, Gema; Catalán, V; Rodríguez, Amaia; et al.
Revista: NUTRIENTS
ISSN 2072-6643  Vol. 11  Nº 2  2019  págs. E454
Obesity favors the development of cardiometabolic alterations such as type 2 diabetes (T2D) and the metabolic syndrome (MS). Obesity and the MS are distinguished by an increase in circulating leptin concentrations, in parallel to a drop in the levels of adiponectin. Consequently, the Adpn/Lep ratio has been suggested as a maker of dysfunctional adipose tissue. We aimed to investigate in humans (n = 292) the reliability of the Adpn/Lep ratio as a biomarker of adipose tissue dysfunction. We considered that an Adpn/Lep ratio of ¿1.0 can be considered normal, a ratio of ¿0.5 <1.0 suggests moderate-medium increased risk, and a ratio of <0.5 indicates a severe increase in cardiometabolic risk. Using these cut-offs, 5%, 54% and 48% of the lean, normoglycemic and without-MS subjects, respectively, fall within the group with an Adpn/Lep ratio below 0.5; while 89%, 86% and 90% of the obese, with T2D and with MS patients fall within the same group (p < 0.001). A significant negative correlation (r = -0.21, p = 0.005) between the Adpn/Lep ratio and serum amyloid A (SAA) concentrations, a marker of adipose tissue dysfunction, was found. We concluded that the Adpn/Lep ratio is a good indicator of a dysfunctional adipose tissue that may be a useful estimator of obesity- and MS-associated cardiometabolic risk, allowing the identification of a higher number of subjects at risk.
Autores: Becerril, Sara; Rodríguez, Amaia; Catalán, V; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 49  Nº Supl. 1  2019  págs. 148 - 149
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 49  Nº Supl. 1  2019  págs. 150
Autores: Gómez-Ambrosi, J; I.González; Catalán, V; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 49  Nº Supl. 1  2019  págs. 147 - 147
Autores: Moncada, Rafael; et al.
Revista: OBESITY SURGERY
ISSN 0960-8923  Vol. 29  Nº Suppl.5  2019  págs. 302 - 302
Autores: Ezquerro, S. ; Mendez-Gimenez, L.; Becerril, Sara; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 49  Nº Supl. 1  2019  págs. 55 - 56
Autores: Valentí, Víctor; Moncada, Rafael; et al.
Revista: OBESITY SURGERY
ISSN 0960-8923  Vol. 29  Nº Supl. 5  2019  págs. 727 - 727
Autores: Ezquerro, S. ; Mocha, F.; Frühbeck, Gema; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 49  Nº Supl. 1  2019  págs. 79 - 80
Autores: Frühbeck, Gema, (Autor de correspondencia)
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 49  Nº Supl. 1  2019  págs. 35 - 35
Autores: Unamuno, X.; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº 9  2018  págs. e12997
Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including type 2 diabetes, cardiovascular diseases, nonalcoholic fatty liver disease and cancer. Adipose tissue is considered one of the largest endocrine organs in the body as well as an active tissue for cellular reactions and metabolic homeostasis rather than an inert tissue for energy storage. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a large number of hormones, cytokines, extracellular matrix proteins and growth and vasoactive factors, collectively termed adipokines that influence a variety of physiological and pathophysiological processes. In the obese state, excessive visceral fat accumulation causes adipose tissue dysfunctionality that strongly contributes to the onset of obesity-related comorbidities. The mechanisms underlying adipose tissue dysfunction include adipocyte hypertrophy and hyperplasia, increased inflammation, impaired extracellular matrix remodelling and fibrosis together with an altered secretion of adipokines. This review describes how adipose tissue becomes inflamed in obesity and summarizes key players and molecular mechanisms involved in adipose inflammation.
Autores: Mendez-Gimenez, L.; Ezquerro, S.; da Silva, I. V. ; et al.
Revista: FRONTIERS IN CHEMISTRY
ISSN 2296-2646  Vol. 6  2018  págs. 99
Aquaporins comprise a family of 13 members of water channels (AQP0-12) that facilitate a rapid transport of water across cell membranes. In some cases, these pores are also permeated by small solutes, particularly glycerol, urea or nitric oxide, among other solutes. Several aquaporins have been identified in the pancreas, an exocrine and endocrine organ that plays an essential role in the onset of insulin resistance and type 2 diabetes. The exocrine pancreas, which accounts for 90% of the total pancreas, secretes daily large volumes of a near-isotonic fluid containing digestive enzymes into the duodenum. AQP1, AQP5, and AQP8 contribute to fluid secretion especially from ductal cells, whereas AQP12 allows the proper maturation and exocytosis of secretory granules in acinar cells of the exocrine pancreas. The endocrine pancreas (10% of the total pancreatic cells) is composed by the islets of Langerhans, which are distributed in alpha, beta, delta, epsilon, and pancreatic polypeptide (PP) cells that secrete glucagon, insulin, somatostatin, ghrelin and PP, respectively. AQP7, an aquaglyceroporin permeated by water and glycerol, is expressed in pancreatic beta-cells and murine studies have confirmed its participation in insulin secretion, triacylglycerol synthesis and proliferation of these endocrine cells. In this regard, transgenic AQP7-knockout mice develop adult-onset obesity, hyperinsulinemia, increased intracellular triacylglycerol content and reduced beta-cell mass in Langerhans islets. Moreover, we have recently reported that AQP7 upregulation in beta-cells after bariatric surgery, an effective weight loss surgical procedure, contributes, in part, to the improvement of pancreatic steatosis and insulin secretion through the increase of intracytoplasmic glycerol in obese rats. Human studies remain scarce and controversial, with some rare cases of loss-of function mutations of the AQP7 gene being associated with the onset of type 2 diabetes. The present Review is focused on the role of aquaporins in the physiology and pathophysiology of the pancreas, highlighting the role of pancreatic AQP7 as a novel player in the control of b-cell function and a potential anti-diabetic-drug.
Autores: Vecchie, A.; Dallegri, F. ; Carbone, F.; et al.
Revista: EUROPEAN JOURNAL OF INTERNAL MEDICINE
ISSN 0953-6205  Vol. 48  2018  págs. 6 - 17
The pro-inflammatory state of the visceral adipose tissue (VAT) is supposed to accelerate cardiovascular (CV) and metabolic diseases in obese subjects. Some studies have recently reported an improved CV prognosis in certain obese and overweight patients as compared with leaner ones. This phenomenon, known as the "obesity paradox" (OP), has been described in many chronic diseases. This narrative review is based on the material searched for and obtained via PubMed and Web of Science up to May 2017. The search terms we used were: "obesity, paradox, adipose tissue" in combination with "cardiovascular, coronary heart disease, heart failure, arrhythmias". Using the current Body Mass Index (BMI)-based obesity definition, individuals with different clinical and biochemical characteristics are gathered together in the same category. Emerging evidence point to the existence of many "Obesity phenotypes" with different association with CV risk, accordingly to physical and life-style features. In this narrative review, we discussed if obesity phenotypes may be associated with a different CV risk, potentially explaining the OP. As a globally accepted definition of obesity is still lacking, we emphasized the need of a new approach, which should consider the heterogeneity of obesity. Better defining "obesities" and related CV risk is critical to markedly improve the classical BMI-based definition of obesity.
Autores:  et al.
Revista: FRONTIERS IN IMMUNOLOGY
ISSN 1664-3224  Vol. 9  2018  págs. 2918
Emerging evidence reveals that adipose tissue-associated inflammation is a main mechanism whereby obesity promotes colorectal cancer risk and progression. Increased inflammasome activity in adipose tissue has been proposed as an important mediator of obesity-induced inflammation and insulin resistance development. Chronic inflammation in tumor microenvironments has a great impact on tumor development and immunity, representing a key factor in the response to therapy. In this context, the inflammasomes, main components of the innate immune system, play an important role in cancer development showing tumor promoting or tumor suppressive actions depending on the type of tumor, the specific inflammasome involved, and the downstream effector molecules. The inflammasomes are large multiprotein complexes with the capacity to regulate the activation of caspase-1. In turn, caspase-1 enhances the proteolytic cleavage and the secretion of the inflammatory cytokines interleukin (IL)-1 beta and IL-18, leading to infiltration of more immune cells and resulting in the generation and maintenance of an inflammatory microenvironment surrounding cancer cells. The inflammasomes also regulate pyroptosis, a rapid and inflammation-associated form of cell death. Recent studies indicate that the inflammasomes can be activated by fatty acids and high glucose levels linking metabolic danger signals to the activation of inflammation and cancer development. These data suggest that activation of the inflammasomes may represent a crucial step in the obesity-associated cancer development. This review will also focus on the potential of inflammasome-activated pathways to develop new therapeutic strategies for the prevention and treatment of obesity-associated colorectal cancer development.
Autores: Spittal, M. J.; Frühbeck, Gema, (Autor de correspondencia)
Revista: LANCET DIABETES AND ENDOCRINOLOGY
ISSN 2213-8587  Vol. 6  Nº 3  2018  págs. 161 - 163
Autores: Frühbeck, Gema, (Autor de correspondencia); Kiortsis, D. N.; Catalán, V;
Revista: LANCET DIABETES AND ENDOCRINOLOGY
ISSN 2213-8587  Vol. 6  Nº 3  2018  págs. 164 - 166
Autores: Unamuno, X.; Frühbeck, Gema, (Autor de correspondencia)
Revista: LANCET
ISSN 0140-6736  Vol. 392  Nº 10161  2018  págs. 2239 - 2240
Autores: Frühbeck, Gema; Badimon, L.;
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl 1  2018  págs. 6 - 7
Autores: Pérez-Pevida, Belén; Diaz-Gutierrez, J.; Miras, A. D.; et al.
Revista: OBESITY
ISSN 1930-7381  Vol. 26  Nº 4  2018  págs. 672 - 682
ObjectiveThe objective of this study was to assess the utility of the 2-hour oral glucose tolerance test (OGTT) value to discriminate between different cardiometabolic profiles and examine the role of body composition in predicting the associated increased risk for glucose impairment, beta-cell dysfunction, and cardiovascular disease (CVD). MethodsSubjects with normal fasting glucose completed a 2-hour OGTT and were categorized to the carbohydrate metabolism alterations (CMAs) or the control group based on a 2-hour glucose threshold of 7.8 mmol/L. Body composition, visceral adipose tissue, OGTT-based parameters, and cardiovascular risk factors (CVRFs) such as hypertension, dyslipidemia, obstructive sleep apnea, nonalcoholic fatty liver disease, and smoking status were measured. ResultsSubjects with CMAs exhibited a significantly higher 1-hour postload glucose level and a greater decline in beta-cell function and CVRF profiles. After multivariate adjustment, an excess of total body and visceral fat was associated with an increased risk of CMAs, beta-cell dysfunction, CVRFs, and lower whole-body insulin sensitivity. ConclusionsThese data support the etiopathogenic role of body and visceral fat in the development of glucose derangements and CVRFs early on in the metabolic dysregulation process. Thus, body composition analysis and OGTT assessment performed in individuals with normal fasting glucose enable a better identification of patients at risk of developing type 2 diabetes and CVD.
Autores: Gómez-Ambrosi, J, (Autor de correspondencia); I.González; Catalán, V; et al.
Revista: CLINICAL NUTRITION
ISSN 0261-5614  Vol. 37  Nº 2  2018  págs. 580 - 589
Background & aims: Visceral adipose tissue (VAT) has been shown to be profoundly responsible of most of the obesity-associated metabolic derangements. The measurement of VAT usually implies the use of imaging techniques such as magnetic resonance imaging or computed tomographi(CT), Our aim was to evaluate the accuracy of the determination of VAT by means of abdominal bioimpedance (BIA) with the ViScan device in comparison with Cr and its clinical usefulness in the management of obesity. Methods: We studied a sample of 140 subjects (73 males/67 females) with BMI ranging from 17.7 to 50.4 kg/m(2) to evaluate the accuracy of the ViScan in comparison to CT to determine VAT. To further analyze ViScan's clinical usefulness we studied a separate cohort (n = 2849) analyzing cardiometabolic risk factors. Furthermore, we studied the ability of the ViScan to detect changes in VAT after weight gain (n = 107) or weight loss (n = 335). The study was performed from October 2009 through June 2015. Results: ViScan determines VAT with a good accuracy in individuals with a CT-VAT up to 200 cm(2), and then with lower precision with increasing body mass, exhibiting a moderate high correlation with Cri VAT (r = 0.75, P < 0.001). Importantly, VAT determination with the ViScan exhibits better correlations with several cardiometabolic risk factors such as glucose, triglycerides, HDL-cholesterol and markers of fatty liver than anthropometric measurements such as BMI or waist circumference. ViScan is able to detect VAT variations after body weight changes. Conclusions: Since the possibility of measuring VAT by imaging techniques is not always available, abdominal BIA represents a good alternative to estimate VAT, allowing the identification of patients with increased VAT-related cardiometabolic risk and a better management of obese patients. (C) 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Autores: Travez, A.; Rabanal-Ruiz, Y. ; Lopez-Alcala, J. ; et al.
Revista: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (ONLINE)
ISSN 1582-4934  Vol. 22  Nº 11  2018  págs. 5648 - 5661
Adipocyte dysfunction in obesity is commonly associated with impaired insulin signalling in adipocytes and insulin resistance. Insulin signalling has been associated with caveolae, which are coated by large complexes of caveolin and cavin proteins, along with proteins with membrane-binding and remodelling properties. Here, we analysed the regulation and function of a component of caveolae involved in growth factor signalling in neuroendocrine cells, neuroendocrine long coiled-coil protein-2 (NECC2), in adipocytes. Studies in 3T3-L1 cells showed that NECC2 expression increased during adipogenesis. Furthermore, NECC2 co-immunoprecipitated with caveolin-1 (CAV1) and exhibited a distribution pattern similar to that of the components of adipocyte caveolae, CAV1, Cavin1, the insulin receptor and cortical actin. Interestingly, NECC2 overexpression enhanced insulin-activated Akt phosphorylation, whereas NECC2 downregulation impaired insulin-induced phosphorylation of Akt and ERK2. Finally, an up-regulation of NECC2 in subcutaneous and omental adipose tissue was found in association with human obesity and insulin resistance. This effect was also observed in 3T3-L1 adipocytes exposed to hyperglycaemia/hyperinsulinemia. Overall, the present study identifies NECC2 as a component of adipocyte caveolae that is regulated in response to obesity and associated metabolic complications, and supports the contribution of this protein as a molecular scaffold modulating insulin signal transduction at these membrane microdomains.
Autores: Frühbeck, Gema; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: METABOLISM-CLINICAL AND EXPERIMENTAL
ISSN 0026-0495  Vol. 87  2018  págs. 123 - 135
Objective: Kallistatin plays an important role in the inhibition of inflammation, oxidative stress, fibrosis and angiogenesis. We aimed to determine the impact of kallistatin on obesity and its associated metabolic alterations as well as its role in adipocyte inflammation and oxidative stress. Methods: Samples obtained from 95 subjects were used in a case-control study. Circulating concentrations and expression levels of kallistatin as well as key inflammation, oxidative stress and extracellular matrix remodelling-related genes were analyzed. Circulating kallistatin concentrations were measured before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB). The impact of kallistatin on lipopolysaccharide (LPS)- and tumour necrosis factor (TNF)-alpha-mediated inflammatory as well as oxidative stress signalling pathways was evaluated. Results: We show that the reduced (P < 0.00001) circulating levels of kallistatin in obese patients increased (P < 0.00001) after RYGB. Moreover, gene expression levels of SERPINA4, the gene coding for kallistatin, were down regulated (P < 0.01) in the liver from obese subjects with non-alcoholic fatty liver disease. Additionally, we revealed that kallistatin reduced (P < 0.05) the expression of inflammation-related genes (CCL2, IL1B, IL6, IL8, TNFA, TGFB) and, conversely, upregulated (P < 0.05) mRNA levels of ADIPOQ and KLF4 in human adipocytes in culture. Kallistatin inhibited (P < 0.05) LPS- and INF-alpha-induced inflammation in human adipocytes via downregulating the expression and secretion of key inflammatory markers. Furthermore, kallistatin also blocked (P < 0.05) TNF-alpha-mediated lipid peroxidation as well as NOX2 and HIF1A expression while stimulating (P < 0.05) the. expression of SIRT1 and FOXO1. Conclusions: These findings provide, for the first time, evidence of a novel role of kallistatin in obesity and its associated comorbidities by limiting adipose tissue inflammation and oxidative stress.
Autores: Moreno-Navarrete, J. M.; Rodríguez, Amaia; Becerril, Sara; et al.
Revista: MOLECULAR NUTRITION AND FOOD RESEARCH
ISSN 1613-4125  Vol. 62  Nº 2  2018 
Scope: To investigate intestinal markers of iron absorption in morbidly obese subjects according to glucose tolerance. Methods and results: Gene expression of both non-heme (SLC40A1 (ferroportin), SLC11A2) and heme iron (SLC46A1 (HCP1), HMOX1) transporters is analyzed in 38 small intestine tissue samples [11 with normal glucose tolerance, 14 with glucose intolerance (GI), and 13 with newly diagnosed type 2 diabetes (T2D)]. SLC40A1 (r = 0.43, p = 0.008) and SLC11A2 (r = 0.35, p = 0.03) mRNA levels are positively correlated with ferritin-to-hepcidin ratio and with fasting glucose, being significantly increased in patients with T2D. Only ferroportin is negatively associated with serum hepcidin (r = -0.617, p < 0.0001). In multivariate regression analysis, fasting glucose contributes independently to intestinal SLC40A1 (p = 0.009) and SLC11A2 (p = 0.04) variance after controlling for age, sex, and BMI. When circulating hepcidin is incorporated into the model, fasting glucose contributes significantly and independently to intestinal SLC40A1 (p = 0.02), but not to SLC11A2 (p = 0.07) variance. SLC46A1 and HMOX1 are similar in all groups. Conclusion: The expression of ferroportin and SLC11A2 is increased in the intestine of patients with T2D in association with iron stores and serum hepcidin levels. Increased intestinal iron absorption is a potential mechanism that could explain the increased body iron stores frequently observed in patients with T2D.
Autores: Becerril, Sara; Rodríguez, Amaia; Catalán, V; et al.
Revista: INTERNATIONAL JOURNAL OF OBESITY
ISSN 0307-0565  Vol. 42  Nº 8  2018  págs. 1458 - 1470
Background/Objectives: Obesity is related to a dynamic extracellular matrix (ECM) remodeling, which involves the synthesis and degradation of different proteins, such as tenascin C (TNC) in the adipose tissue (AT). Given the functional relationship between leptin and inducible nitric oxide synthase (iNOS), our aim was to analyze the impact of the absence of the iNOS gene in AT inflammation and ECM remodeling in ob/ob mice. Subjects/Methods: The expression of genes involved in inflammation and ECM remodeling was evaluated in 10-week-old male double knockout (DBKO) mice simultaneously lacking the ob and iNOS genes as well as in ob/ob mice classified into three groups [control, leptin-treated (1 mg kg(-1) day(-1)) and pair-fed]. Results: Leptin deficiency increased inflammation and fibrosis in AT. As expected, leptin treatment improved the obesity phenotype. iNOS deficiency in ob/ob mice improved insulin sensitivity, AT inflammation, and ECM remodeling, as evidenced by lower AT macrophage infiltration and collagen deposition, a downregulation of proinflammatory and profibrogenic genes Tnf, Emr1, Hif1a, Col6a1, Col6a3, and Tnc, as well as lower circulating TNC levels. Interestingly, leptin upregulated TNC expression and release in 3T3-L1 adipocytes, and iNOS knockdown in 3T3-L1 fat cells produced a significant decrease in basal and leptin-induced Tnc expression. Conclusions: Ablation of iNOS in leptin-deficient mice improved AT inflammation and ECM remodeling-related genes, attenuating fibrosis, and metabolic dysfunction. The activation of iNOS by leptin is necessary for the synthesis and secretion of TNC in adipocytes, suggesting an important role of this alarmin in the development of AT inflammation and fibrosis.
Autores: Burgos-Ramos, E.; Canelles, S. ; Rodríguez, Amaia; et al.
Revista: MOLECULAR AND CELLULAR ENDOCRINOLOGY
ISSN 0303-7207  Vol. 470  2018  págs. 48 - 59
Insulin potentiates leptin effects on muscle accrual and glucose homeostasis. However, the relationship between leptin's central effects on peripheral insulin sensitivity and the associated structural changes remain unclear. We hypothesized that central leptin infusion modifies muscle size through activation of insulin signaling. Muscle insulin signaling, enzymes of fatty acid metabolism, mitochondrial respiratory chain complexes, proliferating cell nuclear antigen (PCNA) and fiber area were analyzed in the gastrocnemius of chronic central infused (L), pair-fed (PF) and control rats. PCNA-positive nuclei, fiber area, GLUT4 and glycogen levels and activation of Akt and mechanistic target of rapamycin were increased in L with no changes in PF. Acetyl-CoA carboxylase-beta mRNA levels and non-esterified fatty acid and triglyceride content were reduced and carnitine palmitoyltransferase-lb expression and mitochondrial complexes augmented in L These results suggest that leptin promotes an increase in muscle size associated with improved insulin signaling favored by lipid profile. (C) 2017 Elsevier B.V. All rights reserved.
Autores: Cheng, Y.; Monteiro, C.; Matos, A.; et al.
Revista: CLINICAL EPIGENETICS (ONLINE)
ISSN 1868-7083  Vol. 10  2018  págs. 54
BACKGROUND: Periprostatic adipose tissue (PPAT) has been recognized to associate with prostate cancer (PCa) aggressiveness and progression. Here, we sought to investigate whether excess adiposity modulates the methylome of PPAT in PCa patients. DNA methylation profiling was performed in PPAT from obese/overweight (OB/OW, BMI¿>¿25 kg m-2) and normal weight (NW, BMI¿<¿25 kg m-2) PCa patients. Significant differences in methylated CpGs between OB/OW and NW groups were inferred by statistical modeling. RESULTS: Five thousand five hundred twenty-six differentially methylated CpGs were identified between OB/OW and NW PCa patients with 90.2% hypermethylated. Four hundred eighty-three of these CpGs were found to be located at both promoters and CpG islands, whereas the representing 412 genes were found to be involved in pluripotency of stem cells, fatty acid metabolism, and many other biological processes; 14 of these genes, particularly FADS1, MOGAT1, and PCYT2, with promoter hypermethylation presented with significantly decreased gene expression in matched samples. Additionally, 38 genes were correlated with antigen processing and presentation of endogenous antigen via MHC class I, which might result in fatty acid accumulation in PPAT and tumor immune evasion. CONCLUSIONS: Results showed that the whole epigenome methylation profiles of PPAT were significantly different in OB/OW compared to normal weight PCa patients. The epigenetic variation associated with excess adiposity likely resulted in altered lipid metabolism and immune dysregulation, contributing towards unfavorable PCa microenvironment, thus warranting further validation studies in larger samples.
Autores: Frühbeck, Gema; Catalán, V; Rodríguez, Amaia; et al.
Revista: ADIPOCYTE
ISSN 2162-3945  Vol. 7  Nº 1  2018  págs. 57 - 62
Obesity is currently the most extended metabolic disturbance worldwide favoring the development of cardiometabolic alterations such as type 2 diabetes, hypertension, and dyslipidemia. Obesity and the metabolic syndrome (MS) are characterized by an increase in circulating leptin concentrations, in parallel to a decrease in blood levels of adiponectin. Consequently, the adiponectin/leptin ratio has been suggested as a maker of adipose tissue dysfunction. This emerging biomarker correlates with insulin resistance better than adiponectin or leptin alone, or even HOMA and is decreased with increasing number of metabolic risk factors having been proposed as a predictive marker for the MS. Moreover, the adiponectin/leptin ratio is negatively correlated with markers of low-grade chronic inflammation. In this sense, an increase in this ratio has been related with reduced atherosclerosis risk as well as with a decreased risk of some types of cancer in epidemiological studies. In this commentary we propose new cutoffs to estimate obesity- and MS-associated cardiometabolic risk according to the adiponectin/leptin ratio and discuss different therapeutic strategies to increase this promising biomarker of metabolic risk.
Autores: Catalán, V, (Autor de correspondencia); Salvador, Francisco Javier; Frühbeck, Gema; et al.
Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
ISSN 1137-6627  Vol. 41  Nº 2  2018  págs. 287 - 289
Autores: Becerril, Sara; Rodríguez, Amaia; Catalán, V; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl 1  2018  págs. 190 - 191
Autores: Ortega, F. J.; Moreno-Navarrete, J. M.; Mercader, J. M.; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl 1  2018  págs. 67
Autores: Landecho, Manuel Fortún; Beloqui, Óscar; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  págs. 210 - 211
Autores: Romero, S.; Frühbeck, Gema; et al.
Revista: JOURNAL OF HEADACHE AND PAIN
ISSN 1129-2369  Vol. 19  Nº Supl. 1  2018  págs. P161
Autores: Gómez-Ambrosi, J; Catalán, V; Rodríguez, Amaia; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  págs. 191 - 192
Autores: Ezquerro, S.; Mendez-Gimenez, L.; Becerril, Sara; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl 1  2018  págs. 190
Autores: Anon-Hidalgo, J.; Catalán, V; Rodríguez, Amaia; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  págs. 69
Autores: Martín, Marina; Rodríguez, Amaia; Gómez-Ambrosi, J; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  págs. 207 - 208
Autores: Rotellar, Fernando; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl 1  2018  págs. 203
Autores: Granero, Lucia; Rotellar, Fernando; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl 1  2018  págs. 202
Autores: Gonzalez-Borja, I. ; Martín, Marina; Rodríguez, Amaia; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  págs. 204 - 205
Autores: Granero, Lucia; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl 1  2018  págs. 202
Autores: Romero, S.; Lainez, J. M.; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl 1  2018  págs. 206 - 207
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  págs. 191
Autores: da Silva, I. V.; Mendez-Gimenez, L.; Camoes, S. P.; et al.
Revista: FREE RADICAL BIOLOGY AND MEDICINE
ISSN 0891-5849  Vol. 120  Nº Supl. 1  2018  págs. S61 - S62
Autores: Rodríguez, Amaia; Mendez-Gimenez, L.; Becerril, Sara; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl 1  2018  págs. 189 - 190
Autores: Unamuno, X.; Becerril, Sara; Rodríguez, Amaia; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl.1  2018  págs. 193 - 194
Autores: Frühbeck, Gema; Rodríguez, Amaia;
Revista: CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE
ISSN 1363-1950  Vol. 20  Nº 5  2017  págs. 402 - 408
Purpose of review A compromised autophagy is associated with the onset of obesity, type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases. Our aim is to review the potential role of ghrelin, a gut hormone involved in energy homeostasis, in the regulation of autophagy. Recent findings In the recent years, it has been demonstrated that autophagy constitutes an important mechanism by which ghrelin exerts a plethora of central and peripheral actions. Ghrelin enhances autophagy through the activation of AMP-activated protein kinase in different target organs to regulate lipid and glucose metabolism, the remodeling and protection of small intestine mucosa, protection against cardiac ischemia as well as higher brain functions such as learning and memory consolidation. Nonetheless, in inflammatory states, such as acute hepatitis, liver fibrosis or adipose tissue inflammation, ghrelin acts as an anti-inflammatory factor reducing the autophagic flux to prevent further cell injury. Interestingly, several cardiometabolic disorders, including obesity, type 2 diabetes, nonalcoholic fatty liver disease or chronic heart failure are accompanied by low ghrelin levels in addition to altered autophagy. Summary Ghrelin represents an attractive target for development of therapeutics for prevention or treatment of metabolic, cardiac or neuronal disorders, in which autophagy is impaired.
Autores: Rodríguez, Amaia; Becerril, Sara; Ezquerro, S.; et al.
Revista: ACTA PHYSIOLOGICA
ISSN 1748-1708  Vol. 219  Nº 2  2017  págs. 362 - 381
Skeletal muscle is the largest organ determining whole-body insulin sensitivity and metabolic homoeostasis. Adaptive changes of skeletal muscle in response to physical activity include adjustments in the production and secretion of muscle-derived bioactive factors, known as myokines, such as myostatin, IL-4, IL-6, IL-7 and IL-15, myonectin, follistatin-like 1 or leukaemia inhibitory factor. These myokines not only act locally in the muscle in an autocrine/paracrine manner, but also are released to the bloodstream as endocrine factors to regulate physiological processes in other tissues. Irisin, derived from the cleavage of FNDC5 protein, constitutes a myokine that induces myogenesis and fat browning (switch of white adipocytes to brown fat-like cells) together with a concomitant increase in energy expenditure. Besides being a target for irisin actions, the adipose tissue also constitutes a production site of FNDC5. Interestingly, irisin secretion from subcutaneous and visceral fat depots is decreased by long-term exercise training and fasting, suggesting a discordant regulation of FNDC5/irisin in skeletal muscle and adipose tissue. Accordingly, our group has recently reported that the adipokine leptin differentially regulates FNDC5/irisin expression in skeletal muscle and fat, confirming the crosstalk between both tissues. Moreover, irisin secretion and function are regulated by other myokines, such as follistatin or myostatin, as well as by other adipokines, including fibroblast growth factor 21 and leptin. Taken together, myokines have emerged as novel molecular mediators of fat browning and their activity can be modulated by adipokines, confirming the crosstalk between skeletal muscle and adipose tissue to regulate thermogenesis and energy expenditure.
Autores: Izaguirre, Maitane; Monreal, José Ignacio; et al.
Revista: CURRENT DIABETES REPORTS
ISSN 1534-4827  Vol. 6  Nº 43  2017 
Recent studies demonstrate that circulating levels of FGF19 are reduced in obesity. In fact, exogenous FGF19 administration is associated with a reduction in food intake as well as with improvements in glycaemia. In contrast, FGF21 levels are elevated in subjects with abdominal obesity, insulin resistance and T2D, probably representing a compensatory response. Additionally, elevated levels of circulating FGF23 in individuals with obesity and T2D are reported in most clinical studies. Finally, increased FGF1 levels in obese patients associated with adipogenesis have been described. FGFs constitute important molecules in the treatment of metabolic diseases due to their beneficial effects on glucose and lipid metabolism. Among all members, FGF19 and FGF21 have demonstrated the ability to improve glucose, lipid and energy homeostasis, along with FGF1, which was recently discovered to have beneficial effects on metabolic homeostasis. Additionally, FGF23 may also play a role in insulin resistance or energy homeostasis beyond mineral metabolism control. These results highlight the relevant use of FGFs as potential biomarkers for the early diagnosis of metabolic diseases. In this regard, notable progress has been made in the development of FGF-based therapies and different approaches are being tested in different clinical trials. However, further studies are needed to determine their potential therapeutic use in the treatment of obesity and obesity-related comorbidities
Autores: Méndez-Giménez, L.; Becerril, Sara; Moncada, Rafael; et al.
Revista: OBESITY SURGERY
ISSN 0960-8923  Vol. 27  Nº 7  2017  págs. 1763 - 1774
BACKGROUND: Gastric plication is a minimally invasive bariatric surgical procedure, where the greater curvature is plicated inside the gastric lumen. Our aims were to analyze the effectiveness of gastric plication on the resolution of obesity, impaired glucose tolerance, and fatty liver in an experimental model of diet-induced obesity (DIO) and to evaluate changes in glycerol metabolism, a key substrate for adiposity and gluconeogenesis, in adipose tissue and the liver. METHODS: Male Wistar DIO rats (n = 58) were subjected to surgical (sham operation and gastric plication) or dietary interventions [fed a normal diet (ND) or high-fat diet (HFD) or pair-fed to the amount of food eaten by gastric-plicated animals]. The expression of aquaglyceroporins (AQPs) in epididymal (EWAT) and subcutaneous (SCWAT) fat and the liver was analyzed by real-time PCR and Western blot. RESULTS: Gastric plication did not result in a significant weight loss in DIO rats, showing a modest reduction in whole-body adiposity and hepatic steatosis. However, gastric-plicated animals exhibited an improvement in basal glycemia and glucose clearance, without changes in hepatic gluconeogenic genes. DIO was associated with an increase in glycerol, higher AQP3 and AQP7 in EWAT and SCWAT, and a decrease in hepatic AQP9. Gastric plication downregulated AQP3 in both fat depots without changes in adipose AQP7 and hepatic AQP9. CONCLUSION: Gastric plication results in a modest reduction in adiposity and hepatosteatosis but restores glycemia by downregulating AQP3, which entails lower efflux of glycerol from fat, lower plasma glycerol availability, and a reduced use of glycerol as a substrate for hepatic gluconeogenesis.
Autores: Méndez-Giménez, L.; Becerril, Sara; Camoes, S. P.; et al.
Revista: INTERNATIONAL JOURNAL OF OBESITY
ISSN 0307-0565  Vol. 41  Nº 9  2017  págs. 1394 - 1402
BACKGROUND/OBJECTIVES: Glycerol is a key metabolite for lipid accumulation in insulin-sensitive tissues as well as for pancreatic insulin secretion. We examined the role of aquaporin-7 (AQP7), the main glycerol channel in beta-cells, and AQP12, an aquaporin related to pancreatic damage, in the improvement of pancreatic function and steatosis after sleeve gastrectomy in diet-induced obese rats. SUBJECTS/METHODS: Male Wistar obese rats (n = 125) were subjected to surgical (sham operation and sleeve gastrectomy) or dietary (pair-fed to the amount of food eaten by sleeve-gastrectomized animals) interventions. The tissue distribution and expression of AQPs in the rat pancreas were analyzed by real-time PCR, western blotting and immunohistochemistry. The effect of ghrelin isoforms and glucagon-like peptide 1 (GLP-1) on insulin secretion, triacylglycerol (TG) accumulation and AQP expression was determined in vitro in RIN-m5F beta-cells. RESULTS: Sleeve gastrectomy reduced pancreatic beta-cell apoptosis, steatosis and insulin secretion. Lower ghrelin and higher GLP-1 concentrations were also found after bariatric surgery. Acylated and desacyl ghrelin increased TG content, whereas GLP-1 increased insulin release in RIN-m5F beta-cells. Sleeve gastrectomy was associated with an upregulation of AQP7 together with a normalization of the increased AQP12 levels in the rat pancreas. Interestingly, ghrelin and GLP-1 repressed AQP7 and AQP12 expression in RINm5F beta-cells. AQP7 protein was negatively correlated with intracellular lipid accumulation in acylated ghrelin-treated cells and with insulin release in GLP-1-stimulated beta-cells. CONCLUSIONS: AQP7 upregulation in beta-cells after sleeve gastrectomy contributes, in part, to the improvement of pancreatic steatosis and insulin secretion by increasing intracellular glycerol used for insulin release triggered by GLP-1 rather than for ghrelin-induced TG biosynthesis.
Autores: Moreno-Navarrete, J. M.; Rodríguez, Amaia; Ortega, F.; et al.
Revista: SCIENTIFIC REPORTS
ISSN 2045-2322  Vol. 7  Nº 1  2017  págs. 5305
Iron status is known to be associated with the physiology of adipose tissue (AT). We aimed to investigate AT heme and expression of heme exporter (FLVCR1) in association with obesity and type 2 diabetes (T2D). Substantial amounts of FLVCR1 mRNA and protein levels were detected in AT, being significantly increased in subjects with T2D, and positively correlated with fasting glucose, fasting triglycerides and with circulating markers of iron stores (serum ferritin, blood hemoglobin and hematocrit). In both visceral (VAT) and subcutaneous AT (SAT), increased heme levels were found in subjects with T2D. Reinforcing these associations, FLVCR1 mRNA levels were positively linked to fasting glucose in an independent cohort. Longitudianlly, the percent change of FLVCR1 positively correlated with the percent change in fasting glucose (r = 0.52, p = 0.03) after bariatric surgery-induced weight loss. High-fat diet-induced weight gain in rats did not result in significant changes in AT Flvcr1 mRNA but, remarkably, the expression of this gene positively correlated with fasting glucose and negatively with insulin sensitivity (QUICKI). Altogether, these findings showed a direct association between FLVCR1 mRNA levels and hyperglycemia, suggesting that increased adipose tissue heme exportation might disrupt, or is the consequence of, impaired systemic glucose metabolism during the progression to T2D.
Autores: Fernandez-Garcia, J. C.; Alcaide, J.; Santiago-Fernandez, C.; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 12  Nº 2  2017  págs. e0171204
Introduction Sensory factors may play an important role in the determination of appetite and food choices. Also, some adipokines may alter or predict the perception and pleasantness of specific odors. We aimed to analyze differences in smell-taste capacity between females with different weights and relate them with fat and fat-free mass, visceral fat, and several adipokines. Materials and methods 179 females with different weights (from low weight to morbid obesity) were studied. We analyzed the relation between fat, fat-free mass, visceral fat (indirectly estimated by bioelectrical impedance analysis with visceral fat rating (VFR)), leptin, adiponectin and visfatin. The smell and taste assessments were performed through the "Sniffin' Sticks" and "Taste Strips" respectively. Results We found a lower score in the measurement of smell (TDI-score (Threshold, Discrimination and Identification)) in obese subjects. All the olfactory functions measured, such as threshold, discrimination, identification and the TDI-score, correlated negatively with age, body mass index (BMI), leptin, fat mass, fat-free mass and VFR. In a multiple linear regression model, VFR mainly predicted the TDI-score. With regard to the taste function measurements, the normal weight subjects showed a higher score of taste functions. However a tendency to decrease was observed in the groups with greater or lesser BMI. In a multiple linear regression model VFR and age mainly predicted the total taste scores. Discussion We show for the first time that a reverse relationship exists between visceral fat and sensory signals, such as smell and taste, across a population with different body weight conditions.
Autores: Álvarez-Sola, G.; Uriarte, Iker; Latasa, María Ujué; et al.
Revista: GUT
ISSN 0017-5749  Vol. 66  Nº 10  2017  págs. 1818 - 1828
Objective Fibroblast growth factor 15/19 (FGF15/19), an enterokine that regulates synthesis of hepatic bile acids (BA), has been proposed to influence fat metabolism. Without FGF15/19, mouse liver regeneration after partial hepatectomy (PH) is severely impaired. We studied the role of FGF15/19 in response to a high fat diet (HFD) and its regulation by saturated fatty acids. We developed a fusion molecule encompassing FGF19 and apolipoprotein A-I, termed Fibapo, and evaluated its pharmacological properties in fatty liver regeneration. Design Fgf15¿/¿ mice were fed a HFD. Liver fat and the expression of fat metabolism and endoplasmic reticulum (ER) stress-related genes were measured. Influence of palmitic acid (PA) on FGF15/19 expression was determined in mice and in human liver cell lines. In vivo half-life and biological activity of Fibapo and FGF19 were compared. Hepatoprotective and proregenerative activities of Fibapo were evaluated in obese db/db mice undergoing PH. Results Hepatosteatosis and ER stress were exacerbated in HFD-fed Fgf15¿/¿ mice. Hepatic expression of Ppar¿2 was elevated in Fgf15¿/¿ mice, being reversed by FGF19 treatment. PA induced FGF15/19 expression in mouse ileum and human liver cells, and FGF19 protected from PA-mediated ER stress and cytotoxicity. Fibapo reduced liver BA and lipid accumulation, inhibited ER stress and showed enhanced half-life. Fibapo provided increased db/db mice survival and improved regeneration upon PH. Conclusions FGF15/19 is essential for hepatic metabolic adaptation to dietary fat being a physiological regulator of Ppar¿2 expression. Perioperative administration of Fibapo improves fatty liver regeneration.
Autores: Moreno Navarrete, J. M.; Ortega, F.; Rodríguez, Amaia; et al.
Revista: DIABETOLOGIA
ISSN 0012-186X  Vol. 60  Nº 5  2017  págs. 915 - 926
Iron excess in adipose tissue is known to promote adipose tissue dysfunction. Here, we aimed to investigate the possible role of haem oxygenase 1 (HMOX1) in iron excess-induced adipose tissue dysfunction. Cross-sectionally, HMOX1 gene expression in subcutaneous and visceral adipose tissue was analysed in two independent cohorts (n = 234 and 40) in relation to obesity. We also evaluated the impact of weight loss (n = 21), weight gain (in rats, n = 20) on HMOX1 mRNA; HMOX1 mRNA levels during human adipocyte differentiation; the effects of inflammation and iron on adipocyte HMOX1; and the effects of HMOX1-induced activity on adipocyte mitochondrial respiratory function, glucose uptake and adipogenesis. Adipose tissue HMOX1 was increased in obese participants (p = 0.01) and positively associated with obesity-related metabolic disturbances, and markers of iron accumulation, inflammation and oxidative stress (p < 0.01). HMOX1 was negatively correlated with mRNAs related to mitochondrial biogenesis, the insulin signalling pathway and adipogenesis (p < 0.01). These associations were replicated in an independent cohort. Bariatric surgery-induced weight loss led to reduced HMOX1 (0.024 +/- 0.010 vs 0.010 +/- 0.004 RU, p < 0.0001), whereas in rats, high-fat diet-induced weight gain resulted in increased Hmox1 mRNA levels (0.22 +/- 0.15 vs 0.54 +/- 0.22 RU, p = 0.005). These changes were in parallel with changes in BMI and adipose tissue markers of iron excess, adipogenesis and inflammation. In human adipocytes, iron excess and inflammation led to increased HMOX1 mRNA levels. HMOX1 induction (by haem arginate [hemin] administration), resulted in a significant reduction of mitochondrial respiratory capacity (including basal respiration and spare respiratory capacity), glucose uptake and adipogenesis in parallel with increased expression of inflammatory- and iron excess-related genes. HMOX1 is an important marker of iron excess-induced adipose tissue dysfunction and metabolic disturbances in human obesity.
Autores: Gómez-Ambrosi, J; Valentí, Víctor; et al.
Revista: INTERNATIONAL JOURNAL OF OBESITY
ISSN 0307-0565  Vol. 41  Nº 9  2017  págs. 1379 - 1387
BACKGROUND/OBJECTIVES: Body weight, body mass index (BMI) and excess weight loss (EWL) are the most frequently used measures to analyse bariatric surgery outcomes. However, these measurements do not provide accurate information on body composition (BC) with body fat (BF), importantly determining the levels of cardiometabolic risk factors. Our aim was to analyse the evolution of BC after Roux-en-Y Gastric Bypass (RYGB) and its influence on the changes of cardiometabolic risk factors in comparison to BMI and EWL. SUBJECTS/METHODS: A group of 81 obese Caucasian patients (19 males/62 females) aged 44.9 +/- 1.3 years undergoing RYGB between January 2006 and December 2011 was prospectively followed up for a period of 3 years. BC was determined by air-displacement plethysmography. Visceral adiposity, physical activity and cardiometabolic risk factors were measured. RESULTS: BF was markedly (P < 0.001) reduced after the first year, increasing progressively during the second and third years after RYGB, following a different trajectory than body weight, BMI and EWL that decreased up to the second year post surgery. Markers of glucose homeostasis decreased during the first month and continued to decrease during the first year (P < 0.05), remaining stabilised or slightly increased between the second and third years following RYGB. However, markers of lipid metabolism decreased (P < 0.05) markedly during the first 12 months, increasing thereafter in parallel to the changes observed in BC, with the exception of high-density lipoprotein-cholesterol, which increased progressively throughout the whole period analysed. CONCLUSIONS: The adverse switch in the changes in BC between the first and the second years after RYGB may underlie the changes observed in cardiometabolic risk factors. Tracking of adiposity during the follow-up of bariatric/metabolic surgery yields clinically relevant information to better identify patients in need of increased lifestyle advice or treatment intensification.
Autores: Moreno-Navarrete, J. M.; Rodríguez, Amaia; Ortega, F.; et al.
Revista: OBESITY
ISSN 1930-7381  Vol. 25  Nº 10  2017  págs. 1723 - 1733
OBJECTIVE: To investigate key enzymes of heme biosynthesis in human adipocytes and adipose tissue (AT). METHODS: Heme biosynthesis-related gene expression (ALAS1, ALAD, HMBS) was investigated in whole AT from humans (n¿=¿178 and n¿=¿75) and rats according to obesity status and during adipogenesis of human preadipocytes. The effects of aminotriazole (an ALAD inhibitor) and of ALAD knockdown were also studied. RESULTS: Consistent heme biosynthesis-related gene expression was detected in both subcutaneous AT (SAT) and visceral AT (VAT) and was significantly increased in SAT. ALAS1, ALAD, and HMBS mRNAs were positively associated with adipogenic gene expression in human AT and significantly decreased in subjects with obesity. These results were replicated in an independent cohort. Both SAT and VAT heme levels were positively correlated with ALAS1, ALAD, and HMBS mRNAs. ALAD and HMBS were mainly expressed in adipocytes and increased during differentiation of human adipocytes in parallel to adipogenic genes. In rats, high-fat diet-induced weight gain resulted in decreased Alad and Hmbs mRNAs in a similar way to what was observed with Adipoq. Aminotriazole administration or ALAD knockdown attenuated adipogenesis in parallel with decreased glucose uptake and impaired mitochondrial respiratory function during human adipocyte differentiation. CONCLUSIONS: Current data suggest a possible role of heme biosynthesis in human adipogenesis
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: ONCOIMMUNOLOGY
ISSN 2162-402X  Vol. 6  Nº 7  2017  págs. e1328338
Growing evidence indicates that adipose tissue inflammation is an important mechanism whereby obesity promotes cancer risk and progression. Since IL-32 is an important inflammatory and remodeling factor in obesity and is also related to colon cancer (CC) development, the aim of this study was to explore whether IL-32 could function as an inflammatory factor in human obesity-associated CC promoting a microenvironment favorable for tumor growth. Samples obtained from 84 subjects [27 lean (LN) and 57 obese (OB)] were used in the study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (49 without CC and 35 with CC). We show, for the first time, that obesity (p = 0.009) and CC (p = 0.026) increase circulating concentrations of IL-32¿. Consistently, we further showed that gene (p < 0.05) and protein (p < 0.01) expression levels of IL-32¿ were upregulated in VAT from obese patients with CC. Additionally, we revealed that IL32 expression levels are enhanced by hypoxia and inflammation-related factors in HT-29 CC cells as well as that IL-32¿ is involved in the upregulation of inflammation (IL8, TNF, and CCL2) and extracellular matrix (ECM) remodeling (SPP1 and MMP9) genes in HT-29 cancer cells. Additionally, we also demonstrate that the adipocyte-conditioned medium obtained from obese patients stimulates (p < 0.05) the expression of IL32 in human CC cells. These findings provide evidence of the potential involvement of IL-32 in the development of obesity-associated CC as a pro-inflammatory and ECM remodeling cytokine.
Autores: Blundell, J. E.; Baker, J. L.; Boyland, E.; et al.
Revista: OBESITY FACTS
ISSN 1662-4025  Vol. 10  Nº 1  2017  págs. 25 - 37
Over the last 10 years the prevalence of obesity across the European continent has in general been rising. With the exception of a few countries where a levelling-off can be perceived, albeit at a high level, this upward trend seems likely to continue. However, considerable country to country variation is noticeable, with the proportion of people with obesity varying by 10% or more. This variation is intriguing and suggests the existence of different profiles of risk or protection factors operating in different countries. The identification of such protection factors could indicate suitable targets for interventions to help manage the obesity epidemic in Europe. This report is the output of a 2-day workshop on the 'Diversity of Obesity in Europe'. The workshop included 14 delegates from 12 different European countries. This report contains the contributions and discussions of the materials and viewpoints provided by these 14 experts; it is not the output of a single mind. However, such is the nature of scientific analysis regarding obesity that it is possible that a different set of 14 experts may have come to a different set of conclusions. Therefore the report should not be seen as a definitive statement of a stable situation. Rather it is a focus for discussion and comment, and a vehicle to drive forward further understanding and management of obesity in Europe.
Autores: Frühbeck, Gema; Catalán, V; Rodríguez, Amaia; et al.
Revista: SCIENTIFIC REPORTS
ISSN 2045-2322  Vol. 7  Nº 1  2017  págs. 2752
The circulating concentrations of adiponectin, an antidiabetic adipokine, have been shown to be reduced in obesity, in relation to an increase in inflammation. The aim of the present work was to assess the effect of leptin replacement on adiponectin levels and expression as well as on markers of oxidative stress and inflammation in leptin-deficient ob/ob mice. Twelve-week-old male mice (n=7-10 per group) were treated with either saline (wild type and ob/ob mice) or leptin (ob/ob mice) for 18 days. A third group of ob/ob mice was treated with saline and pair-fed to the amount of food consumed by the leptin-treated group. Leptin replacement restored values of adiponectin (P < 0.001), reduced circulating 8-isoprostane and serum amyloid A (SAA) levels (P < 0.05 for both), and significantly downregulated the increased gene expression of osteopontin (Spp1, P < 0.05), Saa3 (P < 0.05), Cd68 ( P < 0.01), Il6 (P < 0.01) and NADPH oxidase (Nox1 and Nox2, P < 0.01) in the perirenal WAT and Spp1 (P < 0.05) in the liver of ob/ ob mice. In cultured adipocytes from ob/ ob mice, leptin increased (P < 0.05) the mRNA expression and secretion of adiponectin. We concluded that circulating concentrations of adiponectin are positively regulated by leptin and ameliorate obesity-associated oxidative stress and inflammation in mice.
Autores: Rocha Rodrigues, S.; Rodríguez, Amaia; Becerril, Sara; et al.
Revista: CLINICAL AND EXPERIMENTAL PHARMACOLOGY & PHYSIOLOGY (ONLINE)
ISSN 1440-1681  Vol. 44  Nº 3  2017  págs. 386 - 394
We aimed to investigate the effects of two physical exercise models, voluntary physical activity (VPA) and endurance training (ET) as preventive and therapeutic strategies, respectively, on lipid accumulation regulators and mitochondrial content in VAT of rats fed a high-fat diet (HFD). Sprague-Dawley rats (6weeks old, n=60) were assigned into sedentary and VPA groups fed isoenergetic diets: standard (S, 35kcal% fat) or HFD (71kcal% fat). The VPA groups had free access to wheel running during the entire protocol. After 9weeks, half of the sedentary animals were exercised on a treadmill while maintaining the dietary treatments. The HFD induced no changes in plasma non-esterified fatty acids (NEFA) and glycerol levels and decreased oxidative phosphorylation (OXPHOS) subunit IV and increased truncated/full-length sterol regulatory element-binding transcription factor 1c (SREBP1c) ratio in epididymal white adipose tissue (eWAT). VPA decreased plasma glycerol levels, aquaglyceroporin 7 (AQP7) and increased subunit I of cytochrome c oxidase (COX) protein, in standard diet fed animals. Eight weeks of ET decreased body weight, visceral adiposity and adipocyte size and plasma NEFA and glycerol levels, as well as AQP7 protein expression in eWAT. ET increased fatty acid translocase (FAT/CD36), mitochondrial content of complexes IV and V subunits, mitochondrial biogenesis and dynamic (mitofusins and optic atrophy 1)-related proteins. Moreover, lipogenesis-related markers (SREBP1c and acetyl CoA carboxylase) were reduced after 8weeks of ET. In conclusion, ET-induced alterations reflect a positive effect on mitochondrial function and the overall VAT metabolism of HFD-induced obese rats.
Autores: Latorre, J.; Moreno-Navarrete, J.; Ortega, F.; et al.
Revista: DIABETOLOGIA
ISSN 0012-186X  Vol. 60  Nº Supl 1  2017  págs. S291
Autores: Pérez-Pevida, B. ; Romero, S.; Silva, Camilo; et al.
Revista: DIABETOLOGIA
ISSN 0012-186X  Vol. 60  Nº Supl 1  2017  págs. S571
Autores: Rodríguez, Amaia; Gómez-Ambrosi, J; Catalán, V; et al.
Revista: INTERNATIONAL JOURNAL OF OBESITY
ISSN 0307-0565  Vol. 40  Nº 9  2016  págs. 1405 - 1415
Background/Objectives:Uroguanylin and guanylin are secreted by intestinal epithelial cells as prohormones postprandially and act on the hypothalamus to induce satiety. The impact of obesity and obesity-associated type 2 diabetes (T2D) on proguanylin and prouroguanylin expression/secretion as well as the potential role of guanylin and uroguanylin in the control of lipolysis in humans was evaluated.Subjects/Methods:Circulating and gastrointestinal expression of proguanylin (GUCA2A) and prouroguanylin (GUCA2B) were measured in 134 subjects. In addition, plasma proguanylin and prouroguanylin were measured before and after weight loss achieved either by Roux-en-Y gastric bypass (RYGB) (n=24) or after a conventional diet (n=15). The effect of guanylin and uroguanylin (1¿100¿nmol¿l-1) on lipolysis was determined in vitro in omental adipocytes.Results:Circulating concentrations of prouroguanylin, but not proguanylin, were decreased in obesity in relation to adiposity. Weight loss achieved by RYGB increased plasma proguanylin and prouroguanylin. Obese T2D individuals showed higher expression of intestinal GUCA2A as well as of the receptors of the guanylin system, GUCY2C and GUCY2D, in omental adipocytes. The incubation with guanylin and uroguanylin significantly stimulated lipolysis in differentiated omental adipocytes, as evidenced by hormone-sensitive lipase phosphorylation at Ser563, an increase in fatty acids and glycerol release together with an upregulation of several lipolysis-related genes, including AQP3, AQP7, FATP1 or CD36.Conclusions:Both guanylin and uroguanylin trigger lipolysis in human visceral adipocytes. Given the lipolytic action of the guanylin system on visceral adipocytes, the herein reported decrease of circulating prouroguanylin concentrations in obese patients may have a role in excessive fat accumulation in obesity
Autores: Izaguirre, Maitane; Catalán, V; Frühbeck, Gema;
Revista: ENDOCRINOLOGY
ISSN 0013-7227  Vol. 157  Nº 9  2016  págs. 3391-3
Autores: Ezquerro, S. ; Méndez-Giménez, L.; Becerril, Sara; et al.
Revista: SCIENTIFIC REPORTS
ISSN 2045-2322  Vol. 6  2016  págs. 39942
Bariatric surgery improves non-alcoholic fatty liver disease (NAFLD). Our aim was to investigate the potential role of ghrelin isoforms in the resolution of hepatic steatosis after sleeve gastrectomy, a restrictive bariatric surgery procedure, in diet-induced obese rats. Male Wistar rats (n = 161) were subjected to surgical (sham operation and sleeve gastrectomy) or dietary interventions [fed ad libitum a normal (ND) or a high-fat (HFD) diet or pair-fed]. Obese rats developed hepatosteatosis and showed decreased circulating desacyl ghrelin without changes in acylated ghrelin. Sleeve gastrectomy induced a dramatic decrease of desacyl ghrelin, but increased the acylated/desacyl ghrelin ratio. Moreover, sleeve gastrectomy reduced hepatic triglyceride content and lipogenic enzymes Mogat2 and Dgat1, increased mitochondrial DNA amount and induced AMPK-activated mitochondrial FFA beta-oxidation and autophagy to a higher extent than caloric restriction. In primary rat hepatocytes, the incubation with both acylated and desacyl ghrelin (10, 100 and 1,000 pmol/L) significantly increased TG content, triggered AMPK-activated mitochondrial FFA beta-oxidation and autophagy. Our data suggest that the decrease in the most abundant isoform, desacyl ghrelin, after sleeve gastrectomy contributes to the reduction of lipogenesis, whereas the increased relative acylated ghrelin levels activate factors involved in mitochondrial FFA beta-oxidation and autophagy in obese rats, thereby ameliorating NAFLD.
Autores: Sarah; Susana; Isabel; et al.
Revista: PSYCHONEUROENDOCRINOLOGY
ISSN 0306-4530  Vol. 65  Nº 2016  2016  págs. 102-108
Plasma orexin-A concentrations contribute to poor sleep quality in AN, and both of these variables are associated with therapy response.
Autores: Pascual, Eider; Gómez-Ambrosi, J; Moncada, Rafael; et al.
Revista: OBESITY SURGERY
ISSN 0960-8923  Vol. 26  Nº 8  2016  págs. 1881-9
Our study showed that serum ANGPTL8/betatrophin concentrations were increased in obese subjects after surgically induced weight loss, but not after weight loss achieved by conventional dietary treatment. The change in ANGPTL8/betatrophin concentrations emerged as a significant predictor of the change in HDL-C levels after weight loss.
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: DIABETES
ISSN 0012-1797  Vol. 65  Nº 12  2016  págs. 3636 - 3648
Interleukin (IL)-32 is a recently described cytokine involved in the regulation of inflammation. We aimed to explore whether IL-32 could function as an inflammatory and angiogenic factor in human obesity and obesity-associated type 2 diabetes. Samples obtained from 90 subjects were used in the study. Obese patients exhibited higher expression levels of IL-32 in visceral adipose tissue (AT) as well as in subcutaneous AT and peripheral blood mononuclear cells. IL32 was mainly expressed by stromovascular fraction cells, and its expression was significantly enhanced by inflammatory stimuli and hypoxia, whereas no changes were found after the incubation with anti-inflammatory cytokines. The addition of exogenous IL-32 induced the expression of inflammation and extracellular matrix¿related genes in human adipocyte cultures, and IL32-silenced adipocytes showed a downregulation of inflammatory genes. Furthermore, adipocyte-conditioned media obtained from obese patients increased IL32 gene expression in human monocyte cultures, whereas the adipocyte-conditioned media from lean volunteers had no effect on IL32 mRNA levels. These findings provide evidence, for the first time, about the inflammatory and remodeling properties of IL-32 in AT, implicating this cytokine in obesity-associated comorbidities.
Autores: Moncada, Rafael; Becerril, Sara; Rodríguez, Amaia; et al.
Revista: OBESITY SURGERY
ISSN 0960-8923  Vol. 26  Nº 7  2016  págs. 1537-48
Background: Susceptibility to obesity is associated with a notable inter-individual variation. The aim of the present study was to compare the effectiveness of sleeve gastrectomy (SG) on weight loss and metabolic profile in obesity-prone (OP) rats vs animals that are non-susceptible to obesity (NSO). Methods: Young male Wistar rats (n = 101) were put in a diet-induced obesity (DIO) programme with ad libitum access to a high-fed diet (HFD) during 12 months. Body weight and food intake were regularly registered. Thereafter, rats were ranked by final body weight to identify the obesity-prone (OP) (n = 13) and non-susceptible to obesity (NSO) (n = 14) animals. OP and NSO rats were submitted to surgical interventions (sham operation, SG and pair-fed to the amount of food eaten by sleeve-gastrectomized rats). Body weight, food intake, energy expenditure, body temperature, fat pads weight, and metabolic profiling were analysed 4 weeks after surgical or dietary interventions. Results: SG in both OP and NSO rats decreased body weight as compared to sham and pair-fed groups (P < 0.05), mainly due to reductions in subcutaneous and perirenal fat mass (P < 0.001). Total weight loss achieved in sleeve-gastrectomized OP and NSO rats was higher than that of pair-fed ones (P < 0.05), showing that the SG effect goes beyond caloric restriction. In this regard, sleeve-gastrectomized rats exhibited significantly (P < 0.05) increased basal rectal temperature together with upregulated brown adipose tissue Ucp-1 protein expression levels. A significant (P < 0.05) improvement in insulin sensitivity was also observed in both OP and NSO animals that underwent SG as compared with pair-fed counterparts. Conclusion: Our findings provide the first evidence that obesity-prone rats also benefit from surgery responding effectively to SG, as evidenced by the significant body weight reduction and the metabolic profile improvement.
Autores: Zaida; Monica; et al.
Revista: MOLECULAR NUTRITION & FOOD RESEARCH (ONLINE)
ISSN 1613-4133  Vol. 60  Nº 7  2016  págs. 1673-83
Current data reinforce the impact of TAS2R38 gene on phenotypic and clinical outputs affecting obesity, showing significant associations with extreme weight conditions (i.e., obesity and anorexia nervosa), and changes in both olfactory capacity and immune traits.
Autores: Silva, Camilo; et al.
Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
ISSN 1137-6627  Vol. 39  Nº 1  2016  págs. 23-33
Autores: Moncada, Rafael; Rodríguez, Amaia; Becerril, Sara; et al.
Revista: OBESITY SURGERY
ISSN 0960-8923  Vol. 26  Nº 7  2016  págs. 1549-58
Background Aging and obesity are two conditions associated with increased risk of cardiovascular disease. Our aim was to analyze whether an advanced age affects the beneficial effects of sleeve gastrectomy on weight loss and blood pressure in an experimental model of diet-induced obesity (DIO). Methods Young (6-month-old) and old (18-month-old) male Wistar DIO rats (n¿=¿101) were subjected to surgical (sham operation and sleeve gastrectomy) or dietary interventions (pair-fed to the amount of food eaten by sleeve gastrectomized animals). Systolic (SBP), diastolic (DBP), and mean (MBP) blood pressure values and heart rate (HR) were recorded in conscious, resting animals by non-invasive tail-cuff plethysmography before and 4 weeks after surgical or dietary interventions. Results Aging was associated with higher (P¿<¿0.05) body weight and subcutaneous and perirenal fat mass as well as mild cardiac hypertrophy. Sleeve gastrectomy induced a reduction in body weight, whole-body adiposity, and serum total ghrelin in both young and old DIO rats. The younger group achieved a higher excess weight loss than the older group (164¿±¿60 vs. 82¿±¿17 %, P¿<¿0.05). A significant (P¿<¿0.05) decrease in insulin resistance, SBP, DBP, MBP, and HR without changes in heart weight was observed after sleeve gastrectomy independently of age. Conclusion Our results provide evidence for the effectiveness of sleeve gastrectomy without increased operative risk in body weight and blood pressure reduction
Autores: Conchillo, María de los Ángeles; et al.
Revista: EUROPEAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
ISSN 0954-691X  Vol. 28  Nº 2  2016  págs. 139 - 145
Objective Hypermetabolism in cirrhosis is associated with a high risk of complications and mortality. However, studies about underlying mechanisms are usually focussed on isolated potential determinants and specific etiologies, with contradictory results. We aimed at investigating differences in nutrition, metabolic hormones, and hepatic function between hypermetabolic and nonhypermetabolic men with cirrhosis of the liver. Patients and methods We prospectively enrolled 48 male cirrhotic inpatients. We evaluated their resting energy expenditure (REE) and substrate utilization by indirect calorimetry, body composition by dual-energy X-ray absorptiometry, liver function, and levels of major hormones involved in energy metabolism by serum sample tests. Patients with ascites, specific metabolic disturbances, and hepatocellular carcinoma were excluded. Results REE and REE adjusted per fat-free mass (FFM) were significantly increased in cirrhotic patients. Overall, 58.3% of cirrhotic patients were classified as hypermetabolic. Groups did not differ significantly in age, etiology of cirrhosis, liver function, presence of ascites, use of diuretics, â-blockers, or presence of transjugular intrahepatic portosystemic shunts. Hypermetabolic cirrhotic patients had lower weight, BMI (P< 0.05), nonprotein respiratory quotient (P< 0.01), leptin (P<0.05), and leptin adjusted per fat mass (FM) (P<0.05), but higher FFM% (P< 0.05) and insulin resistance [homeostatic model assessment-insulin resistance (HOMA-IR)] (P<0.05). Only HOMA-IR, leptin/FM, and FFM% were independently related to the presence of hypermetabolism. Conclusion Hypermetabolic cirrhotic men are characterized by lower weight, higher FFM%, insulin resistance, and lower leptin/FM when compared with nonhypermetabolic men. HOMA-IR, FFM%, and leptin/FM were independently associated with hypermetabolism, and may serve as easily detectable markers of this condition in daily clinical practice.
Autores: Gómez-Ambrosi, J; Pascual, Eider; Catalán, V; et al.
Revista: JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN 0021-972X  Vol. 101  Nº 10  2016  págs. 3803-3811
We conclude that serum ANGPTL8/betatrophin concentrations are altered in human dyslipidemia. ANGPTL8/betatrophin emerges as a potential player in dyslipidemia with a strong association with HDL-cholesterol and a potential therapeutic tool for the treatment of dyslipidemia.
Autores: Gómez-Ambrosi, J; Gallego Escuredo, J.; Catalán, V; et al.
Revista: CLINICAL NUTRITION
ISSN 0261-5614  Vol. 36  Nº 3  2016  págs. 861 - 868
BACKGROUND & AIMS: Fibroblast growth factor 19 (FGF19) and 21 (FGF21) have emerged as key regulators of energy homeostasis. Our aim was to analyze the impact of weight loss (WL) induced either by conventional dietary treatment (CDT) or bariatric surgery on FGF19 and FGF21 concentrations. Furthermore, the diverse effect of sleeve gastrectomy (SG) versus RYGB (Roux-en-Y gastric bypass) as two surgical procedures that affect the gastrointestinal anatomy and physiology differently was also analyzed. METHODS: Serum concentrations of FGF19 and FGF21 were measured in 137 obese patients with different degrees of insulin resistance matched by sex, age and body adiposity and compared to 33 lean individuals. Furthermore, FGF19 and FGF21 were measured in 114 subjects before and one-year after WL induced either by CDT (n = 28), SG (n = 20) or RYGB (n = 66). RESULTS: Circulating serum FGF19 concentrations were decreased (P < 0.01) similarly in obese patients regardless of their degree of insulin resistance, while FGF21 levels were increased in obesity (P < 0.01), being further increased in obesity-associated T2D (P < 0.01). FGF19 concentrations were increased in obese subjects after surgically-induced WL (P < 0.01), but not after WL achieved by CDT, while FGF21 levels were reduced after CDT- (P < 0.05) or SG-induced WL (P < 0.05), but not after RYGB. The change in FGF21 concentrations emerged as a significant predictor of the change in insulin resistance (HOMA) after WL. CONCLUSIONS: Based on the circulating concentrations and their subsequent pattern of response following WL, we conclude that FGF19 levels are mainly related to body adiposity, in particular visceral adiposity, while FGF21 is mainly related to glucose homeostasis. CLINICALTRIALS. GOV IDENTIFIER: NCT01572090.
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 11  Nº 9  2016  págs. e0162189
To our knowledge, we herein show for the first time that obese patients with CC exhibit increased circulating levels of OPN, YKL-40 and TNC providing further evidence for the influence of obesity on CC development via ECM proteins, representing promising diagnostic biomarkers or target molecules for therapeutics.
Autores: Pérez-Pevida, Belén; Escalada, J; Romero, S. ; et al.
Revista: DIABETOLOGIA
ISSN 0012-186X  Vol. 59  Nº Supl.1  2016  págs. S142
Autores: Rodríguez, Amaia; Marinelli; Tesse; et al.
Revista: FRONTIERS IN ENDOCRINOLOGY
ISSN 1664-2392  Vol. 6  2015  págs. 171
Gender differences in the relative risk of developing metabolic complications, such as insulin resistance or non-alcoholic fatty liver disease (NAFLD), have been reported. The deregulation of glycerol metabolism partly contributes to the onset of these metabolic diseases, since glycerol constitutes a key substrate for the synthesis of triacylglycerols (TAGs) as well as for hepatic gluconeogenesis. The present mini-review covers the sex--related differences in glycerol metabolism and aquaglyceroporins (AQPs) and its impact in the control of adipose and hepatic fat accumulation as well as in whole-body glucose homeostasis. Plasma glycerol concentrations are increased in women compared to men probably due to the higher lipolytic rate and larger AQP7 amounts in visceral fat as well as the well-known sexual dimorphism in fat mass with women showing higher adiposity. AQP9 represents the primary route for glycerol uptake in hepatocytes, where glycerol is converted by the glycerol-kinase enzyme into glycerol-3-phosphate, a key substrate for de novo synthesis of glucose and TAG. In spite of showing similar hepatic AQP9 protein, women exhibit lower hepatocyte glycerol permeability than men, which might contribute to their lower prevalence of insulin resistance and NAFLD.
Autores: Rodríguez, Amaia; Silvia; Leire; et al.
Revista: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
ISSN 0193-1849  Vol. 309  Nº 8  2015  págs. e691-714
Adipose tissue constitutes an extremely active endocrine organ with a network of signaling pathways enabling the organism to adapt to a wide range of different metabolic challenges, such as starvation, stress, infection, and short periods of gross energy excess. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a huge variety of hormones, cytokines, complement and growth factors, extracellular matrix proteins, and vasoactive factors, collectively termed adipokines. Obesity is associated with adipose tissue dysfunction leading to the onset of several pathologies including type 2 diabetes, dyslipidemia, nonalcoholic fatty liver, or hypertension, among others. The mechanisms underlying the development of obesity and its associated comorbidities include the hypertrophy and/or hyperplasia of adipocytes, adipose tissue inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. Recently, the potential role of brown and beige adipose tissue in the protection against obesity has been also recognized. In contrast to white adipocytes, which store energy in the form of fat, brown and beige fat cells display energy-dissipating capacity through the promotion of triacylglycerol clearance, glucose disposal, and generation of heat for thermogenesis. Identification of the morphological and molecular changes in white, beige, and brown adipose tissue during weight gain is of utmost relevance f
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: GENES AND NUTRITION
ISSN 1555-8932  Vol. 10  Nº 3  2015  págs. 460
Inflammation is a critical contributor to the pathogenesis of metabolic disorders with adipose tissue being crucial in the inflammatory response by releasing multiple adipokines with either pro- or anti-inflammatory activities with potential functions as metabolic regulators. Peripheral blood mononuclear cells (PBMC) have been proposed as representative of the inflammatory status in obesity. The aim of the present study was to evaluate the contribution of PBMC to the obesity-associated chronic inflammation analyzing the expression of novel adipokines. Samples obtained from 69 subjects were used in the study. Real-time PCR determinations were performed to quantify gene expression levels in PBMC of novel adipokines including chemerin, chitinase-3-like protein 1 (YKL-40), lipocalin-2 (LCN-2) and osteopontin (OPN), and their circulating concentrations were also determined by ELISA. We show, for the first time, that PBMC gene expression levels of chemerin (P < 0.0001), chitinase-3-like protein 1 (P = 0.010), lipocalin-2 (P < 0.0001) and osteopontin (P < 0.0001) were strongly upregulated in obesity independently of the glycemic state. Circulating concentrations of these adipokines followed the same trend being significantly higher (P < 0.05) in obese normoglycemic and type 2 diabetic patients compared to lean volunteers and also associated (P < 0.05) with their corresponding mRNA levels in PBMC. These results provide evidence that alterations in inflammation-related adipokines are
Autores: Gómez-Ambrosi, J; Moncada, Rafael; Valentí, Víctor; et al.
Revista: OBESITY SURGERY
ISSN 0960-8923  Vol. 25  Nº 9  2015  págs. 1594-1603
The present study provides evidence for the existence of an adverse cardiometabolic profile in subjects currently considered to be outside traditional NIH guidelines but exhibiting a highly increased adiposity. It is concluded that body composition analysis yields valuable information to be incorporated into indication criteria for BS and that adiposity may be an independent indicator for BS.
Autores: Emma; Sandra; Rodríguez, Amaia; et al.
Revista: MOLECULAR AND CELLULAR ENDOCRINOLOGY
ISSN 0303-7207  Vol. 415  2015  págs. 157-172
Leptin and insulin use overlapping signaling mechanisms to modify hepatic glucose metabolism, which is critical in maintaining normal glycemia. We examined the effect of an increase in central leptin and insulin on hepatic glucose metabolism and its influence on serum glucose levels. Chronic leptin infusion increased serum leptin and reduced hepatic SH-phosphotyrosine phosphatase 1, the association of suppressor of cytokine signaling 3 to the insulin receptor in liver and the rise in glycemia induced by central insulin. Leptin also decreased hepatic phosphoenolpyruvate carboxykinase levels and increased insulin's ability to phosphorylate insulin receptor substrate-1, Akt and glycogen synthase kinase on Ser9 and to stimulate glucose transporter 2 and glycogen levels. Peripheral leptin treatment reproduced some of these changes, but to a lesser extent. Our data indicate that leptin increases the hepatic response to a rise in insulin, suggesting that pharmacological manipulation of leptin targets may be of interest for controlling glycemia.
Autores: Rodríguez, Amaia; Becerril, Sara; Leire; et al.
Revista: INTERNATIONAL JOURNAL OF OBESITY
ISSN 0307-0565  Vol. 39  Nº 3  2015  págs. 397-407
Taken together, our results provide evidence for a regulatory role of leptin on FNDC5/irisin, favoring muscle accretion but reducing fat browning
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: GENES AND NUTRITION
ISSN 1555-8932  Vol. 10  Nº 3  2015  págs. 460
Inflammation is a critical contributor to the pathogenesis of metabolic disorders with adipose tissue being crucial in the inflammatory response by releasing multiple adipokines with either pro- or anti-inflammatory activities with potential functions as metabolic regulators. Peripheral blood mononuclear cells (PBMC) have been proposed as representative of the inflammatory status in obesity. The aim of the present study was to evaluate the contribution of PBMC to the obesity-associated chronic inflammation analyzing the expression of novel adipokines. Samples obtained from 69 subjects were used in the study. Real-time PCR determinations were performed to quantify gene expression levels in PBMC of novel adipokines including chemerin, chitinase-3-like protein 1 (YKL-40), lipocalin-2 (LCN-2) and osteopontin (OPN), and their circulating concentrations were also determined by ELISA. We show, for the first time, that PBMC gene expression levels of chemerin (P < 0.0001), chitinase-3-like protein 1 (P = 0.010), lipocalin-2 (P < 0.0001) and osteopontin (P < 0.0001) were strongly upregulated in obesity independently of the glycemic state. Circulating concentrations of these adipokines followed the same trend being significantly higher (P < 0.05) in obese normoglycemic and type 2 diabetic patients compared to lean volunteers and also associated (P < 0.05) with their corresponding mRNA levels in PBMC. These results provide evidence that alterations in inflammation-related adipokines are
Autores: Gallego-Escuredo J; Gómez-Ambrosi, J; Catalán, V; et al.
Revista: INTERNATIONAL JOURNAL OF OBESITY
ISSN 0307-0565  Vol. 39  Nº 1  2015  págs. 121-9
Obesity is characterized by reciprocal alterations in FGF19 (decrease) and FGF21 (increase) levels. Although worsened in diabetic obese patients, obesity itself appears as the predominant determinant of the abnormalities in FGF21 and FGF19 levels. Opposite changes in ß-Klotho expression in fat and liver indicate potential tissue-specific alterations in the responsiveness to endocrine FGFs in obesity
Autores: Lancha, Andoni; Santiago; Rodríguez, Amaia; et al.
Revista: ARCHIVES OF MEDICAL RESEARCH
ISSN 0188-4409  Vol. 46  Nº 1  2015  págs. 47-53
Increased STX8 expression in VAT appears to be associated with the presence of T2D in obese patients through a mechanism that may involve GLUT4.
Autores: Rodríguez, Amaia; Natalia; Inma; et al.
Revista: SCIENTIFIC REPORTS
ISSN 2045-2322  Vol. 5  2015  págs. 12067
Glycerol is an important metabolite for the control of lipid accumulation in white adipose tissue (WAT) and liver. We aimed to investigate whether exogenous administration of leptin improves features of non-alcoholic fatty liver disease (NAFLD) in leptin-deficient ob/ob mice via the regulation of AQP3 and AQP7 (glycerol channels mediating glycerol efflux in adipocytes) and AQP9 (aquaglyceroporin facilitating glycerol influx in hepatocytes). Twelve-week-old male wild type and ob/ob mice were divided in three groups as follows: control, leptin-treated (1 mg/kg/d) and pair-fed. Leptin deficiency was associated with obesity and NAFLD exhibiting an AQP3 and AQP7 increase in WAT, without changes in hepatic AQP9. Adipose Aqp3 and hepatic Aqp9 transcripts positively correlated with markers of adiposity and hepatic steatosis. Chronic leptin administration (4-weeks) was associated with improved body weight, whole-body adiposity, and hepatosteatosis of ob/ob mice and to a down-regulation of AQP3, AQP7 in WAT and an up-regulation of hepatic AQP9. Acute leptin stimulation in vitro (4-h) induced the mobilization of aquaglyceroporins towards lipid droplets (AQP3) and the plasma membrane (AQP7) in murine adipocytes. Our results show that leptin restores the coordinated regulation of fat-specific AQP7 and liver-specific AQP9, a step which might prevent lipid overaccumulation in WAT and liver in obesity
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: ACTA DIABETOLOGICA
ISSN 0940-5429  Vol. 52  Nº 2  2015  págs. 257-266
The ribosomal protein S6 kinase 1 (S6K1) is a component of the insulin signalling pathway that has been proposed as a key molecular factor in insulin resistance development under conditions of nutrient overload. The aim was to evaluate the involvement of S6K1 in obesity as well as to explore their association with visceral adipose tissue (VAT) inflammation. Samples obtained from 40 subjects were used. Gene expression levels of RPS6KB1 and key inflammatory markers were analysed in VAT. The effect of insulin on transcript levels of RPS6KB1 in human differentiated adipocytes was also explored. RPS6KB1 mRNA levels in VAT were increased (P < 0.05) in obese patients. Insulin treatment significantly enhanced (P < 0.01) gene expression levels of RPS6KB1 and a positive association (P < 0.05) of RPS6KB1 expression with different markers of insulin resistance was observed. Moreover, RPS6KB1 gene expression levels were positively correlated with VAT gene expression levels of the inflammatory markers CCL2, CD68, MMP2, MMP9, VEGFA and CHI3L1 as well as with mRNA levels of MTOR and MAPK8, representative players involved in signalling pathways related to S6K1. The increased levels of S6K1 in obesity and its positive association with insulin resistance and inflammation suggest a role for this protein in the changes that take place in VAT in obesity establishing a link between inflammation and a higher risk for the development of metabolic
Autores: Méndez-Giménez, L.; Becerril, Sara; Moncada, Rafael; et al.
Revista: OBESITY SURGERY
ISSN 0960-8923  Vol. 25  Nº 9  2015  págs. 1723 - 1734
BACKGROUND: Glycerol constitutes an important metabolite for the control of lipid accumulation and glucose homeostasis. Our aim was to investigate the potential role of aquaglyceroporins, which are glycerol channels mediating glycerol efflux in adipocytes (AQP3 and AQP7) and glycerol influx (AQP9) in hepatocytes, in the improvement of adiposity and hepatic steatosis after sleeve gastrectomy in an experimental model of diet-induced obesity (DIO). METHODS: Male Wistar DIO rats (n = 161) were subjected to surgical (sham operation and sleeve gastrectomy) or dietary interventions [fed ad libitum a normal diet (ND) or a high-fat diet (HFD) or pair-fed to the amount of food eaten by sleeve-gastrectomized animals]. The tissue distribution and expression of AQPs in biopsies of epididymal (EWAT) and subcutaneous (SCWAT) white adipose tissue and liver were analyzed by real-time PCR, Western blot, and immunohistochemistry. RESULTS: Four weeks after surgery, DIO rats undergoing sleeve gastrectomy showed a reduction in body weight, whole-body adiposity, and hepatic steatosis. DIO was associated with a tendency towards an increase in EWAT AQP3 and SCWAT AQP7 and a decrease in hepatic AQP9. Sleeve gastrectomy downregulated AQP7 in both fat depots and upregulated AQP3 in EWAT, without changing hepatic AQP9. Aqp7 transcript levels in EWAT and SCWAT were positively associated with adiposity and glycemia, while Aqp9 mRNA was negatively correlated with markers of hepatic steatosis and insulin resistance. CONCLUSION: Our results show, for the first time, that sleeve gastrectomy, a widely applied bariatric surgery procedure, restores the coordinated regulation of fat-specific AQP7 and liver-specific AQP9, thereby improving whole-body adiposity and hepatic steatosis.
Autores: Gómez-Ambrosi, J; Catalán, V; Rodríguez, Amaia; et al.
Revista: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
ISSN 0735-1097  Vol. 65  Nº 6  2015  págs. 622-623
Autores: Pérez-Pevida, Belén; Pascual, Eider; et al.
Revista: ENDOCRINOLOGIA Y NUTRICION
ISSN 1575-0922  Vol. 62  2015  págs. 106 - 107
Autores: Pascual, Eider; Galofre, Juan Carlos; Pérez-Pevida, Belén; et al.
Revista: ENDOCRINOLOGIA Y NUTRICION
ISSN 1575-0922  Vol. 62  Nº Supl  2015  págs. 20
Autores: Pérez-Hernández, AI; Catalán, V; Gómez-Ambrosi, J; et al.
Revista: FRONTIERS IN ENDOCRINOLOGY
ISSN 1664-2392  Vol. 5  2014  págs. 65
Obesity constitutes one of the most important metabolic diseases being associated to insulin resistance development and increased cardiovascular risk. Association between obesity and cancer has also been well established for several tumor types, such as breast cancer in post-menopausal women, colorectal, and prostate cancer. Cancer is the first death cause in developed countries and the second one in developing countries, with high incidence rates around the world. Furthermore, it has been estimated that 15-20% of all cancer deaths may be attributable to obesity. Tumor growth is regulated by interactions between tumor cells and their tissue microenvironment. In this sense, obesity may lead to cancer development through dysfunctional adipose tissue and altered signaling pathways. In this review, three main pathways relating obesity and cancer development are examined: (i) inflammatory changes leading to macrophage polarization and altered adipokine profile; (ii) insulin resistance development; and (iii) adipose tissue hypoxia. Since obesity and cancer present a high prevalence, the association between these conditions is of great public health significance and studies showing mechanisms by which obesity lead to cancer development and progression are needed to improve prevention and management of these diseases.
Autores: Leire; Rodríguez, Amaia; Inma; et al.
Revista: MOLECULAR AND CELLULAR ENDOCRINOLOGY
ISSN 0303-7207  Vol. 397  Nº 1-2  2014  págs. 78-92
Aquaglyceroporins and caveolins are submicroscopic integral membrane proteins that are particularly abundant in many mammalian cells. Aquaglyceroporins (AQP3, AQP7, AQP9 and AQP10) encompass a subfamily of aquaporins that allow the movement of water, but also of small solutes, such as glycerol, across cell membranes. Glycerol constitutes an important metabolite as a substrate for de novo synthesis of triacylglycerols and glucose as well as an energy substrate to produce ATP via the mitochondrial oxidative phosphorylation. In this sense, the control of glycerol influx/efflux in metabolic organs by aquaglyceroporins plays a crucial role with the dysregulation of these glycerol channels being associated with metabolic diseases, such as obesity, insulin resistance, non-alcoholic fatty liver disease and cardiac hypertrophy. On the other hand, caveolae have emerged as relevant plasma membrane sensors implicated in a wide range of cellular functions, including endocytosis, apoptosis, cholesterol homeostasis, proliferation and signal transduction. Caveolae-coating proteins, namely caveolins and cavins, can act as scaffolding proteins within caveolae by concentrating signaling molecules involved in free fatty acid and cholesterol uptake, proliferation, insulin signaling or vasorelaxation, among others. The importance of caveolae in whole-body homeostasis is highlighted by the link between homozygous mutations in genes encoding caveolins and cavins with metabolic diseases, such as lipo
Autores: Frühbeck, Gema; Méndez-Giménez, L.; Fernández-Formoso, J. A.; et al.
Revista: NUTRITION RESEARCH REVIEWS
ISSN 0954-4224  Vol. 27  Nº 1  2014  págs. 63 - 93
In adipocytes the hydrolysis of TAG to produce fatty acids and glycerol under fasting conditions or times of elevated energy demands is tightly regulated by neuroendocrine signals, resulting in the activation of lipolytic enzymes. Among the classic regulators of lipolysis, adrenergic stimulation and the insulin-mediated control of lipid mobilisation are the best known. Initially, hormone-sensitive lipase (HSL) was thought to be the rate-limiting enzyme of the first lipolytic step, while we now know that adipocyte TAG lipase is the key enzyme for lipolysis initiation. Pivotal, previously unsuspected components have also been identified at the protective interface of the lipid droplet surface and in the signalling pathways that control lipolysis. Perilipin, comparative gene identification-58 (CGI-58) and other proteins of the lipid droplet surface are currently known to be key regulators of the lipolytic machinery, protecting or exposing the TAG core of the droplet to lipases. The neuroendocrine control of lipolysis is prototypically exerted by catecholaminergic stimulation and insulin-induced suppression, both of which affect cyclic AMP levels and hence the protein kinase A-mediated phosphorylation of HSL and perilipin. Interestingly, in recent decades adipose tissue has been shown to secrete a large number of adipokines, which exert direct effects on lipolysis, while adipocytes reportedly express a wide range of receptors for signals involved in lipid mobilisation. Recently recognised mediators of lipolysis include some adipokines, structural membrane proteins, atrial natriuretic peptides, AMP-activated protein kinase and mitogen-activated protein kinase. Lipolysis needs to be reanalysed from the broader perspective of its specific physiological or pathological context since basal or stimulated lipolytic rates occur under diverse conditions and by different mechanisms.
Autores: Gómez-Ambrosi, J; Pascual, Eider; Catalán, V; et al.
Revista: JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN 0021-972X  Vol. 99  Nº 10  2014  págs. e2004-e2009
We conclude that serum betatrophin is decreased in human obesity, being further reduced in obesity-associated insulin resistance. Betatrophin levels are closely related to obesity-associated cardiometabolic risk factors, emerging as a potential biomarker of insulin resistance and T2D.
Autores: Rodríguez, Amaia; Gena, P.; Méndez Giménez, L.; et al.
Revista: INTERNATIONAL JOURNAL OF OBESITY
ISSN 0307-0565  Vol. 38  Nº 9  2014  págs. 1213 - 1220
Background/Objectives:Glycerol represents an important metabolite for the control of lipid accumulation and hepatic gluconeogenesis. We investigated whether hepatic expression and functionality of aquaporin-9 (AQP9), a channel mediating glycerol influx into hepatocytes, is impaired in non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in the context of insulin resistance.Subjects/Methods:Liver biopsies were obtained from 66 morbid obese patients undergoing bariatric surgery (66% women, mean body mass index (BMI) 46.1±1.0 kg m-2) with available liver echography and pathology analysis of the biopsies in this cross-sectional study. Subjects were classified according to normoglycemia (NG), impaired glucose tolerance (IGT) or type 2 diabetes (T2D). Hepatic expression of AQP9 was analyzed by real-time PCR, western blotting and immunohistochemistry, while glycerol permeability (P gly) was measured by stopped-flow light scattering.Results:AQP9 was the most abundantly (P<0.0001) expressed aquaglyceroporin in human liver (AQP9>>>AQP3>AQP7>AQP10). Obese patients with T2D showed increased plasma glycerol as well as lower P gly and hepatic AQP9 expression. The prevalence of NAFLD and NASH in T2D patients was 100 and 65%, respectively. Interestingly, AQP9 expression was decreased in patients with NAFLD and NASH as compared with those without hepatosteatosis, in direct relation to the degree of steatosis and lobular inflammation, being further reduced in insulin-resistant individuals. The association of AQP9 with insulin sensitivity was independent of BMI and age. Consistent with these data, fasting insulin and C-reactive protein contributed independently to 33.1% of the hepatic AQP9 mRNA expression variance after controlling for the effects of age and BMI.Conclusions:AQP9 downregulation together with the subsequent reduction in hepatic glycerol permeability in insulin-resistant states emerges as a compensatory mechanism whereby the liver counteracts further triacylglycerol accumulation within its parenchyma as well as reduces hepatic gluconeogenesis in patients with NAFLD.
Autores:  Naukkarinen ; Heinonen; Hakkarainen; et al.
Revista: DIABETOLOGIA
ISSN 0012-186X  Vol. 57  Nº 1  2014  págs. 167-176
Our results suggest that maintenance of high mitochondrial transcription and lack of inflammation in SAT are associated with low liver fat and MHO.
Autores: Rocío; Ortega; Rodríguez, Amaia; et al.
Revista: INTERNATIONAL JOURNAL OF OBESITY
ISSN 0307-0565  Vol. 38  Nº 12  2014  págs. 1545-54
These findings show, for the first time, that HMGB1 expression and release by human adipocytes is altered by inflammatory conditions as those imposed by obesity and insulin resistance. Our data reveal a novel role for HMGB1 as a stimulatory factor of insulin secretion of ß-pancreatic cells.
Autores: Gómez-Ambrosi, J; Catalán, V; Rodríguez, Amaia; et al.
Revista: DIABETES CARE
ISSN 0149-5992  Vol. 37  Nº 10  2014  págs. 2813-2821
The current study provides evidence for the existence of a comparable adverse cardiometabolic profile in MHO and MAO patients; thus the MHO concept should be applied with caution. A better identification of the obesity phenotypes and a more precise diagnosis are needed for improving the management of obese individuals.
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN 0021-972X  Vol. 99  Nº 8  2014  págs. E1407 - E1417
CONTEXT: Wingless-type mouse mammary tumor virus integration site family (WNT)-5A is a glycoprotein involved in the regulation of the inflammatory response by activating the noncanonical Wnt signaling pathway. Secreted frizzled-related protein (SFRP)-5 acts as a decoy receptor that binds and sequesters WNT5A, preventing activation of frizzled receptors and attenuating the noncanonical Wnt signaling. OBJECTIVE: The aim of the study was to evaluate the involvement of WNT5A and SFRP5 in obesity and obesity-related comorbidities as well as to explore their effect in visceral adipose tissue inflammation. PATIENTS AND METHODS: Samples obtained from 90 subjects were used. Circulating and gene expression levels of WNT5A and SFRP5 were analyzed in different metabolic tissues. The effect of TNF-¿ and lipopolysaccharide on the transcript levels of WNT5A and SFRP5 in adipocytes was explored. We also investigated whether WNT5A itself can activate an inflammatory response. RESULTS: Increased circulating levels of WNT5A in obese patients (P < .05) were decreased (P < .001) after gastric bypass. In this line, WNT5A mRNA in visceral adipose tissue was increased (P < .05) in obese patients with gene expression levels of SFRP5 being down-regulated (P < .05). WNT5A mRNA expression was significantly enhanced (P < .01) by lipopolysaccharide and TNF-¿ treatment, whereas no effects were found in SFRP5 gene expression levels. Furthermore, exogenous WNT5A induced (P < .05) IL-6, IL1B, MMP2, MMP9, and SSP1 mRNA expression in human adipocyte cultures. CONCLUSIONS: Activation of noncanonical Wnt signaling through the up-regulation of WNT5A and down-regulation of SFRP5 may promote a proinflammatory state in visceral adipose tissue contributing to the development of obesity-associated comorbidities.
Autores: Moreno-Navarrete, JM; Novelle, MG; Catalán, V; et al.
Revista: DIABETES CARE
ISSN 0149-5992  Vol. 37  Nº 4  2014  págs. 1092-100
Circulating markers of iron overload are associated with insulin resistance. Less is known about the impact of iron overload on adipose tissue (AT). We hypothesized that gene expression markers of iron metabolism in AT could be associated with insulin action. RESEARCH DESIGN AND METHODS The AT expression of ferroportin (SLC40A1), transferrin (TF), TF receptor (TFRC), ferritin (FT) heavy polypeptide 1 (FTH1), and FT light polypeptide (FTL) was analyzed cross-sectionally in three independent cohorts and also after weight loss-induced changes in insulin sensitivity (clamp M value) in an independent fourth cohort. RESULTS In human AT, TF mRNA and protein levels were decreased with obesity and insulin resistance in the three cohorts and were positively associated with adipogenic mRNAs and insulin action. Otherwise, FTL mRNA and protein and SLC40A1 transcripts were positively associated with BMI and negatively linked to adipogenic genes and insulin action. Bariatric surgery-induced weight loss led to increased TF and decreased TFRC, FTH1, FTL, and SLC40A1 in subcutaneous AT in parallel to improved insulin action. CONCLUSIONS These results suggest that iron overload impacts on AT in association with insulin resistance.
Autores: Lancha, Andoni; Moncada, Rafael; Valentí, Víctor; et al.
Revista: OBESITY SURGERY
ISSN 0960-8923  Vol. 24  2014  págs. 1702-1708
Circulating OPN levels decreased with HFD feeding remaining unaltered after SG. The expression of Spp1 in EWAT and liver was not modified by SG. The global improvement of metabolism after SG appears not to involve changes in serum OPN concentrations as well as in EWAT and liver expression in rats.
Autores: Sini; Lilli; Naukkarinen; et al.
Revista: INTERNATIONAL JOURNAL OF OBESITY
ISSN 0307-0565  Vol. 38  Nº 11  2014  págs. 1423-1431
Together, hypertrophy and hypoplasia in acquired obesity are related to metabolic dysfunction, possibly through disturbances in mitochondrial function and increased cell death within the adipose tissue.
Autores: Lucas, E. ; Jurado-Pueyo, M. ; Fortuño, María Antonia; et al.
Revista: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
ISSN 0925-4439  Vol. 1842  Nº 12 Pt A  2014  págs. 2448 - 2456
G protein-coupled receptor kinase 2 (GRK2) has recently emerged as a negative modulator of insulin signaling. GRK2 downregulation improves insulin sensitivity and prevents systemic insulin resistance. Cardiac GRK2 levels are increased in human heart failure, while genetically inhibiting GRK2 leads to cardioprotection in mice. However, the molecular basis underlying the deleterious effects of GRK2 up-regulation and the beneficial effects of its inhibition in the heart are not fully understood. Therefore, we have explored the interconnections among a systemic insulin resistant status, GRK2 dosage and cardiac insulin sensitivity in adult (9 month-old) animals. GRK2(+/-) mice display enhanced cardiac insulin sensitivity and mild heart hypertrophy with preserved systolic function. Cardiac gene expression is reprogrammed in these animals, with increased expression of genes related to physiological hypertrophy, while the expression of genes related to pathological hypertrophy or to diabetes/obesity co-morbidities is repressed. Notably, we find that cardiac GRK2 levels increase in situations where insulin resistance develops, such as in ob/ob mice or after high fat diet feeding. Our data suggest that GRK2 downregulation/inhibition can help maintain cardiac function in the face of co-morbidities such as insulin resistance, diabetes or obesity by sustaining insulin sensitivity and promoting a gene expression reprogramming that confers cardioprotection.
Autores: Lancha, Andoni; Rodríguez, Alfredo; Catalán, V; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 9  Nº 5  2014  págs. e98398
Osteopontin (OPN) is a multifunctional extracellular matrix (ECM) protein involved in multiple physiological processes. OPN expression is dramatically increased in visceral adipose tissue in obesity and the lack of OPN protects against the development of insulin resistance and inflammation in mice. We sought to unravel the potential mechanisms involved in the beneficial effects of the absence of OPN. We analyzed the effect of the lack of OPN in the development of obesity and hepatic steatosis induced by a high-fat diet (HFD) using OPN-KO mice. OPN expression was upregulated in epididymal white adipose tissue (EWAT) and liver in wild type (WT) mice with HFD. OPN-KO mice had higher insulin sensitivity, lower body weight and fat mass with reduced adipose tissue ECM remodeling and reduced adipocyte size than WT mice under a HFD. Reduced MMP2 and MMP9 activity was involved in the decreased ECM remodeling. Crown-like structure number in EWAT as well as F4/80-positive cells and Emr1 expression in EWAT and liver increased with HFD, while OPN-deficiency blunted the increase. Moreover, our data show for the first time that OPN-KO under a HFD mice display reduced fibrosis in adipose tissue and liver, as well as reduced oxidative stress in adipose tissue. Gene expression of collagens Col1a1, Col6a1 and Col6a3 in EWAT and liver, as well as the profibrotic cytokine Tgfb1 in EWAT were increased with HFD, while OPN-deficiency prevented this increase. OPN deficiency prevented hepatic steatosis via reduction in the expression of molecules involved in the onset of fat accumulation such as Pparg, Srebf1, Fasn, Mogat1, Dgat2 and Cidec. Furthermore, OPN-KO mice exhibited higher body temperature and improved BAT function. The present data reveal novel mechanisms of OPN in the development of obesity, pointing out the inhibition of OPN as a promising target for the treatment of obesity and fatty liver.
Autores: Lancha, Andoni; Moncada, Rafael; Valentí, Víctor; et al.
Revista: SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
ISSN 0930-2794  Vol. 28  Nº 2  2014  págs. 2412 - 2420
Background Bariatric surgery (BS) has proven to be an effective treatment for morbid obesity. Osteopontin (OPN) is a proinflammatory cytokine involved in the development of obesity. The aim of our study was to determine the effect of weight loss following BS on circulating levels of OPN in humans. Methods Body composition and circulating concentrations of OPN and markers of bone metabolism were determined in obese patients who underwent Roux-en-Y gastric bypass (RYGB; n = 40) or sleeve gastrectomy (SG; n = 11). Results Patients who underwent RYGB or SG showed decreased body weight (P < 0.001) and body fat percentage (P < 0.001) as well as lower insulin resistance. However, plasma OPN levels were significantly increased after RYGB (P < 0.001) but remained unchanged following SG (P = 0.152). Patients who underwent RYGB also showed significantly increased C-terminal telopeptide of type-I collagen (ICTP) (P < 0.01) and osteocalcin (P < 0.001) while bone mineral density tended to decrease (P = 0.086). Moreover, OPN concentrations were positively correlated with the bone resorption marker ICTP after surgery. On the other hand, patients who underwent SG showed significantly increased ICTP levels (P < 0.05), and the change in OPN was positively correlated with the change in ICTP and negatively with the change in vitamin D after surgery (P < 0.05). Conclusions RYGB increased circulating OPN levels, while they remained unaltered after SG. The increase in OPN levels after RYGB could be related to the increased bone resorption in relation to its well-known effects on bone of this malabsorptive procedure in comparison to the merely restrictive SG.
Autores: Pascual, Eider; Pérez-Pevida, Belén; et al.
Revista: ENDOCRINOLOGIA Y NUTRICION
ISSN 1575-0922  Nº 61  2014  págs. 108
Autores: Pascual, Eider; Pérez-Pevida, Belén; et al.
Revista: ENDOCRINOLOGIA Y NUTRICION
ISSN 1575-0922  Vol. 61  2014  págs. 112
Autores: Pascual, Eider; Pérez-Pevida, Belén; et al.
Revista: ENDOCRINE ABSTRACTS
ISSN 1470-3947  Vol. 35  2014 
Obstructive sleep apnoea (OSA) is very common in severe obese patients and has been related to insulin resistance (IR) and hyperleptinemia, and these findings may have effects on food behavior and obesity complications. In order to explore this relationship and the role of sex we have studied 531 patients with morbid obesity (BMI 42.8+6.5 kg/m2). A full polysomnographic study and glucose, insulin and leptin measurements as well as air displacement plethysmography were performed in all of them. Ninety-six obese patients (BMI 45,8+7.3 kg/m2) with OSA were evaluated before and immediately after nocturnal CPAP treatment for 24 h. About 370 out of 531 patients had OSA (AHI 37.7+28/h). OSA patients had higher glucose (108+29 vs 99+26 mg/dl.P<0.001), insulin plasma levels (20+12 vs 16+10 (mu/l.P<0.001) and HOMA index (HOMAi) values (5.5+4.1 vs 4+2.8.P<0.001), but lower leptin levels (45.4+27 vs 55.5+28 ng/ml.P<0.001) and lower fat mass (48.9+7.5 vs 50.5+6.6%.P<0.05) than non-OSA patients. When compared with basal conditions, as a whole group (n=96) CPAP administration was followed by a reduction in glucose (108.3+29.4 vs 115+33.7.P<0.001), and insulin values (21.4+16.4 vs 23.8+16.3 mU/l.P<0.01) without any change in leptin concentrations (49.9+31.3 vs 50+32.3 mU/l. P=NS). Male patients (n=52) showed reductions in glucose values (109.1+22.3 vs 116+26.3 mg/dl.P<0.01) and HOMAi (5.8+3.2 vs 7+4.9.P<0.05). However, no changes either in glucose (PreM: 112+49.7 vs 114+52 mg/dl.P=NS), insulin values or HOMAi (5.1+3.9 vs 6.4+4.8.P=NS) were seen in PreM women following CPAP. In contrast, postmenopausal women (PostM; n=21) showed a reduction in glucose (102.9+17.8 vs 113+28.8 mg/dl.P<0.01), insulin (18.1+11.3 vs 23.5+17.5 mU/L.P<0.05) and HOMAi (4.9+4.2 vs 7.1+8.1.P<0.05) with no variation in leptin values (67+25.3 vs 65+31.9 ng/ml.P=NS) after CPAP. There was no correlation between reduction in apnoea index and decrease in HOMA index after CPAP in any of the subgroups. These data indicate that either OSA in itself or its correction by CPAP has no effects on leptin secretion in patients with morbid obesity. Globally, OSA potentiates IR, but acute correction of OSA by CPAP has more beneficial effects in PostM women and men than in PreM women.
Autores: Becerril, Sara; Gómez-Ambrosi, J; Martín, Marina; et al.
Revista: HISTOLOGY AND HISTOPATHOLOGY
ISSN 0213-3911  Vol. 28  Nº 13  2013  págs. 1411-1425
From a histological and functional point of view, two types of adipose tissue can be identified. As opposed to the mainly unilocular white adipocytes, brown adipocytes possess plenty of small multilocular lipid droplets and dissipate energy as heat. Moreover, two distinct types of brown adipose cells exist. In vivo fate mapping experiments of brown adipose tissue (BAT) precursors suggest that classical brown adipocytes and skeletal myoblasts originate from a common mesenchymal, myogenic factor 5 (Myf5)-positive precursor cell. In addition to the classical brown adipocytes, thermogenic brown-like adipocytes (brite/beige cells) may appear within white adipose tissue (WAT) depots, sharing many of the morphological and functional features of brown adipocytes, but arising from a Myf5-negative lineage. In humans, the conversion of white fat cells into brite adipocytes could be a strategy to increase energy expenditure. The zinc finger transcription factor Prdm16 controls the bidirectional fate decision between brown adipocytes and myoblasts. Prdm16 determines the brown fat-like programme and thermogenesis in both brown and white adipose tissues. Moreover, the expression of this transcriptional regulator is strongly correlated with beige cell-selective genes. From a therapeutical point of view, the potential of inducing BAT or the transdifferentiation of WAT into beige cells by enhancing Prdm16 expression, as well as the identification of mechanisms of Prdm16 function and regulation represent potentially exciting new approaches for treatment or prevention of obesity and related diseases.
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: FRONTIERS IN PHYSIOLOGY
ISSN 1664-042X  Vol. 2  Nº 4  2013  págs. 275
Inflammation and altered immune response are important components of obesity and contribute greatly to the promotion of obesity-related metabolic complications, especially cancer development. Adipose tissue expansion is associated with increased infiltration of various types of immune cells from both the innate and adaptive immune systems. Thus, adipocytes and infiltrating immune cells secrete pro-inflammatory adipokines and cytokines providing a microenvironment favorable for tumor growth. Accumulation of B and T cells in adipose tissue precedes macrophage infiltration causing a chronic low-grade inflammation. Phenotypic switching toward M1 macrophages and Th1 T cells constitutes an important mechanism described in the obese state correlating with increased tumor growth risk. Other possible synergic mechanisms causing a dysfunctional adipose tissue include fatty acid-induced inflammation, oxidative stress, endoplasmic reticulum stress, and hypoxia. Recent investigations have started to unravel the intricacy of the cross-talk between tumor cell/immune cell/adipocyte. In this sense, future therapies should take into account the combination of anti-inflammatory approaches that target the tumor microenvironment with more sophisticated and selective anti-tumoral drugs.
Autores:  et al.
Título: Obstructive
Revista: JOURNAL OF CLINICAL SLEEP MEDICINE
ISSN 1550-9389  Vol. 9  Nº 11  2013  págs. 1165-71
Morbid obesity is frequently associated with abnormal LVM, particularly in patients with OSA; this association is independent of HT, BMI, body composition, and other clinical factors, supporting a direct role of OSA on LVM in morbid obesity. This suggests that OSA and LVM might be taken as predictors of the cardiovascular risk in these patients.
Autores: Gena; Mastrodonato; Portincasa; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 8  Nº 10  2013  págs. e78139
One form of liver steatosis, namely Non-Alcoholic Fatty Liver Disease (NAFLD), is a worrisome health problem worldwide characterized by intrahepatic triacylglycerol (TG) overaccumulation. NAFLD is a common feature of metabolic syndrome being often associated with obesity, dyslipidemia and diabetes and mostly closely linked to insulin resistance. The mechanism of NAFLD pathogenesis is object of intense investigation especially regarding complex systems ultimately resulting in excessive TG deposition in hepatocytes. However, scarce is the attention about the relevance of hepatic import of glycerol, the other primary source (as glycerol-3-phosphate) of increased TG in hepatocytes. Obese leptin-deficient (ob/ob) mice, an animal model of NAFLD, were used to evaluate the functional involvement of Aquaporin-9 (AQP9), the major pathway of liver glycerol entry, in hepatosteatosis. By RT-PCR and qPCR, the level of Aqp9 mRNA in the liver of starved obese mice was comparable with the corresponding control lean littermates. By immunoblotting, the AQP9 protein at the hepatocyte sinusoidal plasma membrane of obese mice was markedly lower (33%) than lean mice, a finding fully confirmed by immunohistochemistry. By stopped-flow light scattering, the liver glycerol permeability of ob/ob mice was significantly lower (53%) than lean mice, a finding consistent with both the observed down-regulation of AQP9 protein and increased level of plasma glycerol characterizing obese mice. In summary, our re
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: SURGERY FOR OBESITY AND RELATED DISEASES
ISSN 1550-7289  Vol. 9  Nº 2  2013  págs. 306-314
The increased levels of chemerin in obesity and its positive association with inflammation suggest a role for this chemoattractant protein in the changes that take place in visceral adipose tissue in the presence of energy surplus, establishing a link between inflammation and the greater risk of the development of metabolic disease.
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: EUROPEAN JOURNAL OF NUTRITION
ISSN 1436-6207  Vol. 52  Nº 6  2013  págs. 1587-1595
These findings represent the first observation that STEAP4 and NGAL mRNA and protein levels in human VAT are related to iron status. Moreover, STEAP4 and NGAL are associated with pro-inflammatory markers suggesting their potential involvement in the low-grade chronic inflammation accompanying obesity.
Autores: Moreno-Navarrete, JM; Touskova, V; Sabater, M; et al.
Revista: INTERNATIONAL JOURNAL OF OBESITY
ISSN 0307-0565  Vol. 37  Nº 9  2013  págs. 1230-37
Liver, but not adipose tissue, might be the source of increased circulating PEDF linked to insulin resistance.
Autores: Ortega, F; Mercader, JM; Catalán, V; et al.
Revista: CLINICAL CHEMISTRY
ISSN 0009-9147  Vol. 59  Nº 5  2013  págs. 781-92
Circulating miRNAs are deregulated in severe obesity. Weight loss-induced changes in this profile and the study of in silico targets support this observation and suggest a potential mechanistic relevanc
Autores: Pascual, Eider; et al.
Revista: ENDOCRINOLOGIA Y NUTRICION
ISSN 1575-0922  Vol. 60  2013  págs. 91
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: HISTOLOGY AND HISTOPATHOLOGY
ISSN 0213-3911  Vol. 27  Nº 12  2012  págs. 1515-1528
Adipose tissue responds dynamically to alterations in nutrient excess through adipocyte hypertrophy and hyperplasia, followed by increased angiogenesis, immune cell infiltration, extracellular matrix (ECM) overproduction, and thus, increased production of proinflammatory adipokines during the progression of chronic inflammation. Adipose tissue remodelling is an ongoing process that is pathologically accelerated in the obese state in large part mediated by ECM proteins and proteases. The ECM is subject to major modifications by adipocytes and other cell types that are infiltrated in the adipose tissue, such as macrophages and vascular cells. In obesity, unusual expression of ECM components and fragments derived from tissue-remodelling processes can influence immune cell recruitment and activation, actively contributing to inflammation. ECM turnover requires a tightly regulated balance between the synthesis of the components and their proteolysis, mainly by fibrinolytic systems and matrix metalloproteases (MMPs). In this review, we discuss the key cellular steps that lead to adipose tissue remodelling and the main molecular mechanisms and mediators in this process. We highlight the importance of hypoxia and angiogenesis in the adipose remodelling process, as well as the cross-talk between adipocytes, macrophages and ECM components
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: Journal of Clinical Endocrinology & Obesity
ISSN 0021-972X  Vol. 97  Nº 10  2012  págs. e1880 - e1889
Autores: Ribeiro, R; Monteiro, C; Catalán, V; et al.
Revista: BMC MEDICINE
ISSN 1741-7015  Vol. 10  2012  págs. 108
Obesity and excess adiposity modified the expression of PP adipose tissue genes to ultimately foster fat mass growth. In patients with prostate cancer the expression profile of PP adipose tissue accounted for hypercellularity and reduced immunosurveillance. Both findings may be liable to promote a favorable environment for prostate cancer progression.
Autores: Fagundo, A. B.; De La Torre, R.; Jimenez-Murcia, S.; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 7  Nº 8  2012 
Background: Extreme weight conditions (EWC) groups along a continuum may share some biological risk factors and intermediate neurocognitive phenotypes. A core cognitive trait in EWC appears to be executive dysfunction, with a focus on decision making, response inhibition and cognitive flexibility. Differences between individuals in these areas are likely to contribute to the differences in vulnerability to EWC. The aim of the study was to investigate whether there is a common pattern of executive dysfunction in EWC while comparing anorexia nervosa patients (AN), obese subjects (OB) and healthy eating/weight controls (HC). Methods: Thirty five AN patients, fifty two OB and one hundred thirty seven HC were compared using the Wisconsin Card Sorting Test (WCST); Stroop Color and Word Test (SCWT); and Iowa Gambling Task (IGT). All participants were female, aged between 18 and 60 years. Results: There was a significant difference in IGT score (F(1.79); p<.001), with AN and OB groups showing the poorest performance compared to HC. On the WCST, AN and OB made significantly more errors than controls (F(25.73); p<.001), and had significantly fewer correct responses (F(2.71); p<.001). Post hoc analysis revealed that the two clinical groups were not significantly different from each other. Finally, OB showed a significant reduced performance in the inhibition response measured with the Stroop test (F(5.11); p<.001) compared with both AN and HC. Conclusions: These findings suggest that EWC subjects (namely AN and OB) have similar dysfunctional executive profile that may play a role in the development and maintenance of such disorders.
Autores: Rodríguez, Amaia; Becerril, Sara; Valentí, Víctor; et al.
Revista: OBESITY SURGERY
ISSN 0960-8923  Vol. 22  Nº 11  2012  págs. 1786 - 1787
Autores: Gómez-Ambrosi, J; Silva, Camilo; Catalán, V; et al.
Revista: DIABETES CARE
ISSN 0149-5992  Vol. 35  Nº 2  2012  págs. 383-88
CUN-BAE is an easy-to-apply predictive equation that may be used as a first screening tool in clinical practice. Furthermore, our equation may be a good tool for identifying patients at cardiovascular and type 2 diabetes risk.
Autores: Rodríguez, Amaia; Becerril, Sara; Valentí, Víctor; et al.
Revista: OBESITY SURGERY
ISSN 0960-8923  Vol. 22  Nº 9  2012  págs. 1481 - 1490
Sleeve gastrectomy constitutes an effective surgical procedure for the treatment of morbid obesity. The aim of the present study was to establish the effects of sleeve gastrectomy and caloric restriction on weight loss and cardiovascular parameters in diet-induced obese (DIO) rats. Male Wistar DIO rats were subjected to surgical interventions (n = 30) (sham operation, sleeve gastrectomy, or pair-fed to the amount of food eaten by sleeve-gastrectomized animals and compared to lean control rats) or dietary interventions (n = 40) (fed ad libitum a normal diet (ND) or a high-fat diet or an ND with a caloric restriction of 25 %). Systolic blood pressure (SBP), diastolic blood pressure, and mean blood pressure values and heart rate (HR) were recorded in conscious, resting animals by noninvasive tail-cuff plethysmography before and 3 weeks after surgical or dietary interventions. Both sleeve gastrectomy and caloric restriction induced a reduction in body weight, whole-body adiposity, and serum leptin together with an increased excess weight loss in DIO rats. Sleeve gastrectomy was further associated with an improvement in insulin resistance and the lipid profile, as well as with a reduction in serum ghrelin levels. A decrease in HR and heart weight was observed in caloric-restricted groups. Sleeve-gastrectomized rats not only exhibited a reduction in HR (a dagger HR = -45 +/- 19 bpm) but also in SBP values (a dagger SBP = -22 +/- 10 mmHg) compared to the DIO rats (a dagger SBP = 14 +/- 8 mmHg). Our findings provide evidence that the beneficial effects of sleeve gastrectomy on blood pressure values are beyond weight loss in rats with diet-induced obesity.
Autores: Rodríguez, Amaia; Gómez-Ambrosi, J; Catalán, V; et al.
Revista: Diabetologia
ISSN 0012-186X  Vol. 55  Nº 11  2012  págs. 3038 - 3050
Autores: Álvarez-Cienfuegos, Francisco Javier; Valentí, Víctor; Muñoz, Miguel Ángel; et al.
Revista: ENDOSCOPY
ISSN 0013-726X  Vol. 44  Nº Suppl. 2  2012  págs. UCTN:E366-7
Autores: Martín, Marina; Burrell, María Ángela; Gómez-Ambrosi, J; et al.
Revista: OBESITY SURGERY
ISSN 0960-8923  Vol. 22  Nº 4  2012  págs. 634 - 640
Background: Sleeve gastrectomy (SG) has been used as a multipurpose surgical procedure for the treatment of morbid obesity. The aim of the study was to analyze gastric morphology and histology at two different time points after SG in rats. Methods: Thirty-five male Wistar rats were fed ad libitum during 3 months on a high-fat diet to induce obesity. Subsequently, 25 diet-induced obese rats underwent either SG (n=12) or a sham operation (n=13). The remaining ten obese animals encompassed the nonoperated control group (Co). Four weeks postoperatively, 15 rats (n05 rats/experimental group) were sacrificed, while the remaining 20 rats were sacrificed after 16 weeks (animals/group; Co=5, sham=8, SG=7) to compare the gastric morphological and histopathological changes over time. Body weight and food intake were regularly recorded. Results: For both time periods, the Co groups exhibited the highest body weight, while the rats undergoing the SG showed the lowest weight gain (P<0.05). Initially, significant differences (P<0.005) in food intake relative to body weight were observed between the Co rats and animals undergoing surgery, which disappeared thereafter. The actual total stomach sizeafter both experimental periods in the SG group was similar to that of non- and sham-operated rats mainly due to a forestomach enlargement, which was more pronounced after 16 weeks. Traits of gastritis cystica profunda characterized by gastric foveolae elongation with hyperplasia and cystic dilatation of the glandswere observed in the residual stomachs of the sleeve-gastrectomized rats. These findings were mostly observed after 16 weeks of performing the SG, although they were also detected occasionally following 4 weeks postoperatively. No intestinal metaplasia was observed. Conclusion: After SG gastric macro- and microscopic changes with functional implications in both the short and long term take place.
Autores: Ortega, F. J.; Moreno-Navarrete, J. M.; Mayas, D.; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 7  Nº 5  2012 
Context: Expression and activity of the main lipogenic enzymes is paradoxically decreased in obesity, but the mechanisms behind these findings are poorly known. Breast Cancer 1 (BrCa1) interacts with acetyl-CoA carboxylase (ACC) reducing the rate of fatty acid biosynthesis. In this study, we aimed to evaluate BrCa1 in human adipose tissue according to obesity and insulin resistance, and in vitro cultured adipocytes. Research Design and Methods: BrCa1 gene expression, total and phosphorylated (P-) BrCa1, and ACC were analyzed in adipose tissue samples obtained from a total sample of 133 subjects. BrCa1 expression was also evaluated during in vitro differentiation of human adipocytes and 3T3-L1 cells. Results: BrCa1 gene expression was significantly up-regulated in both omental (OM; 1.36-fold, p = 0.002) and subcutaneous (SC; 1.49-fold, p = 0.001) adipose tissue from obese subjects. In parallel with increased BrCa1 mRNA, P-ACC was also up-regulated in SC (p = 0.007) as well as in OM (p = 0.010) fat from obese subjects. Consistent with its role limiting fatty acid biosynthesis, both BrCa1 mRNA (3.5-fold, p<0.0001) and protein (1.2-fold, p = 0.001) were increased in pre-adipocytes, and decreased during in vitro adipogenesis, while P-ACC decreased during differentiation of human adipocytes (p = 0.005) allowing lipid biosynthesis. Interestingly, BrCa1 gene expression in mature adipocytes was restored by inflammatory stimuli (macrophage conditioned medium), whereas lipogenic genes significantly decreased. Conclusions: The specular findings of BrCa1 and lipogenic enzymes in adipose tissue and adipocytes reported here suggest that BrCa1 might help to control fatty acid biosynthesis in adipocytes and adipose tissue from obese subjects.
Autores: Valle, A; Catalán, V; Rodríguez, Amaia; et al.
Revista: LIVER INTERNATIONAL
ISSN 1478-3223  Vol. 32  Nº 6  2012  págs. 951-61
The results suggest alterations in mitochondrial function and methionine metabolism as potential contributing factors to increased oxidative stress in liver of obese diabetic patients which may be influencing the development of NAFLD and NASH.
Autores: Moreno-Navarrete, JM; Catalán, V; White, L; et al.
Revista: DIABETES
ISSN 0012-1797  Vol. 61  Nº 2  2012  págs. 281-91
GPR55 is a putative cannabinoid receptor, and l-¿-lysophosphatidylinositol (LPI) is its only known endogenous ligand. We investigated 1) whether GPR55 is expressed in fat and liver; 2) the correlation of both GPR55 and LPI with several metabolic parameters; and 3) the actions of LPI on human adipocytes. We analyzed CB1, CB2, and GPR55 gene expression and circulating LPI levels in two independent cohorts of obese and lean subjects, with both normal or impaired glucose tolerance and type 2 diabetes. Ex vivo experiments were used to measure intracellular calcium and lipid accumulation. GPR55 levels were augmented in the adipose tissue of obese subjects and further so in obese patients with type 2 diabetes when compared with nonobese subjects. Visceral adipose tissue GPR55 correlated positively with weight, BMI, and percent fat mass, particularly in women. Hepatic GPR55 gene expression was similar in obese and type 2 diabetic subjects. Circulating LPI levels were increased in obese patients and correlated with fat percentage and BMI in women. LPI increased the expression of lipogenic genes in visceral adipose tissue explants and intracellular calcium in differentiated visceral adipocytes. These findings indicate that the LPI/GPR55 system is positively associated with obesity in humans
Autores: Gómez-Ambrosi, J; Silva, Camilo; Galofre, Juan Carlos; et al.
Revista: INTERNATIONAL JOURNAL OF OBESITY
ISSN 0307-0565  Vol. 36  Nº 2  2012  págs. 286 - 294
Autores: Becerril, Sara; Rodríguez, Amaia; Catalán, V; et al.
Revista: PHYSIOLOGICAL GENOMICS (ONLINE)
ISSN 1531-2267  Vol. 44  Nº 13  2012  págs. 678-688
Leptin and nitric oxide (NO) are implicated in the control of energy homeostasis. The aim of the present study was to examine the impact of the absence of the inducible NO synthase (iNOS) gene on the regulation of energy balance in ob/ob mice analyzing the changes in gene expression levels in brown adipose tissue (BAT). Double knockout (DBKO) mice simultaneously lacking the ob and iNOS genes were generated and the expression of genes involved in energy balance including fatty acid and glucose metabolism as well as mitochondrial genes were analyzed by microarrays. DBKO mice exhibited an improvement in energy balance with a decrease in body weight (P < 0.001), total fat pads (P < 0.05) and food intake (P < 0.05) as well as an enhancement in BAT function as compared to ob/ob mice. To better understand the molecular events associated with this improvement, BAT gene expression was analyzed. Of particular interest, gene expression levels of the key subunit of the Mediator complex Med1 was upregulated (P < 0.05) in DBKO mice. Real-Time PCR and immunohistochemistry further confirmed this data. Med1 is implicated in adipogenesis, lipid metabolic and biosynthetic processes, glucose metabolism and mitochondrial metabolic pathways. Med1 plays an important role in the transcriptional control of genes implicated in energy homeostasis, suggesting that the improvement in energy balance and BAT function of the DBKO mice is mediated, at least in part, through the transcription coactivator Med1.
Autores: Rodríguez, Amaia; Becerril, Sara; Valentí, Víctor; et al.
Revista: OBESITY SURGERY
ISSN 0960-8923  Vol. 22  Nº 2  2012  págs. 309-315
Sleeve gastrectomy constitutes an effective surgical procedure for the treatment of morbid obesity in humans and rodents with diet-induced obesity. The aim of the present study was to establish the effects of sleeve gastrectomy on weight loss and cardiovascular parameters in genetically obese (fa/fa) Zucker rats. Eleven-week-old male obese (fa/fa) (n = 20) Zucker rats were assigned to three alternative procedures (sham operation, sleeve gastrectomy, or pair-fed to the amount of food eaten by sleeve-gastrectomized animals) and compared with lean Zucker (Fa/Fa) rats (n = 9). Systolic (SBP), diastolic (DBP), and mean (MBP) blood pressure values as well as heart rate (HR) were recorded in conscious, resting animals by non-invasive tail-cuff plethysmography before and 3 weeks after the surgical interventions. Sleeve-gastrectomized rats experienced a reduction in body weight (P < 0.01), total adiposity amounts (P < 0.001), together with an increased excess weight loss (%EWL) (P < 0.05) compared with sham-operated and pair-fed animals 3 weeks after the surgical interventions. Rats with sleeve gastrectomy exhibited reduced (P < 0.01) blood pressure values (Delta SBP = -11 +/- 8 mmHg; Delta DBP = -6 +/- 4 mmHg; Delta MBP = -8 +/- 6 mmHg) compared with the control group, but no changes were observed in HR (P = 0.560). Sham-operated and pair-fed groups did not alter their cardiovascular variables. Our findings provide evidence of the beneficial effects of sleeve gastrectomy on blood pressure values in addition to the weight loss in obese (fa/fa) Zucker rats independently of surgical trauma and food intake reduction.
Autores: Sáinz Amillo, N.; Rodríguez, Amaia; Catalán, V; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 7  Nº 1  2012  págs. e29389
Leptin improves insulin sensitivity in skeletal muscle. Our goal was to determine whether proteins controlling GLUT4 traffic are altered by leptin deficiency and in vivo leptin administration in skeletal muscle of wild type and ob/ob mice. Leptin-deficient ob/ob mice were divided in three groups: control, leptin-treated (1 mg/kg/d) and leptin pair-fed ob/ob mice. Microarray analysis revealed that 1,546 and 1,127 genes were regulated by leptin deficiency and leptin treatment, respectively. Among these, we identified 24 genes involved in intracellular vesicle-mediated transport in ob/ob mice. TBC1 domain family, member 1 (Tbc1d1), a negative regulator of GLUT4 translocation, was up-regulated (P¿=¿0.001) in ob/ob mice as compared to wild types. Importantly, leptin treatment reduced the transcript levels of Tbc1d1 (P<0.001) and Tbc1d4 (P¿=¿0.004) in the leptin-treated ob/ob as compared to pair-fed ob/ob animals. In addition, phosphorylation levels of TBC1D1 and TBC1D4 were enhanced in leptin-treated ob/ob as compared to control ob/ob (P¿=¿0.015 and P¿=¿0.023, respectively) and pair-fed ob/ob (P¿=¿0.036 and P¿=¿0.034, respectively) mice. Despite similar GLUT4 protein expression in wild type and ob/ob groups a different immunolocalization of this protein was evidenced in muscle sections. Leptin treatment increased GLUT4 immunoreactivity in gastrocnemius and extensor digitorum longus sections of leptin-treated ob/ob mice. Moreover, GLUT4 protein detected in immunoprecipitates from TBC1D4 was reduced by leptin replacement compared to control ob/ob (P¿=¿0.013) and pair-fed ob/ob (P¿=¿0.037) mice. Our findings suggest that leptin enhances the intracellular GLUT4 transport in skeletal muscle of ob/ob animals by reducing the expression and activity of the negative regulators of GLUT4 traffic TBC1D1 and TBC1D4.
Autores: Álvarez-Cienfuegos, Francisco Javier; Valentí, Víctor; Muñoz, Miguel Ángel; et al.
Revista: ENDOSCOPY
ISSN 0013-726X  Vol. 44  Nº Supl. 2  2012  págs. E366 - E367
Autores: Rodríguez, Amaia; Catalán, V; Gómez-Ambrosi, J; et al.
Revista: CELL CYCLE
ISSN 1538-4101  Vol. 10  Nº 10  2011  págs. 1548 - 1556
Autores: Ortega, FJ; Moreno-Navarrete, JM; Sabater, M; et al.
Revista: EUROPEAN JOURNAL OF ENDOCRINOLOGY
ISSN 0804-4643  Vol. 165  Nº 4  2011  págs. 639 - 645
Autores: Rodríguez, Amaia; Catalán, V; Gómez-Ambrosi, J; et al.
Revista: JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN 0021-972X  Vol. 96  Nº 4  2011  págs. 586 - 597
Autores: Gómez-Ambrosi, J; Silva, Camilo; Galofre, Juan Carlos; et al.
Revista: OBESITY
ISSN 1930-7381  Vol. 19  Nº 7  2011  págs. 1439 - 1444
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: MOLECULAR MEDICINE
ISSN 1076-1551  Vol. 17  Nº 11-12  2011  págs. 1157-67
Calprotectin has been recently described as a novel marker of obesity. The aim of this study was to determine the circulating concentrations and expression levels of calprotectin subunits (S100A8 and S100A9) in visceral adipose tissue (VAT), exploring its impact on insulin resistance and inflammation and the effect of weight loss. We included 53 subjects in the study. Gene expression levels of the S100A8/A9 complex were analyzed in VAT as well as in both adipocytes and stromovascular fraction cells (SVFCs). In addition, circulating calprotectin and soluble receptor for the advanced glycation end product (sRAGE) concentrations were measured before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 26). Circulating concentrations and VAT expression of S100A8/A9 complex were increased in normoglycemic and type 2 diabetic obese patients (P < 0.01) and associated with markers of inflammation (P < 0.01). Oppositely, concentrations of sRAGE were significantly lower (P < 0.001) in both obese groups compared to lean volunteers. Elevated calprotectin levels in obese patients decreased (P < 0.00001) after RYGB, whereas sRAGE concentrations tended to increase. Calprotectin was mainly expressed by SVFCs, and its expression was significantly correlated (P < 0.01) with mRNA levels of the monocyte-macrophage-related molecules macrophage-specific antigen CD68 (CD68), monocyte chemotactic protein 1 (MCP1), integrin ¿-M (CD11B), and NADPH oxidase 2 (NOX2). Tumor necrosis fac
Autores: Pulido, MR; Díez-Ruiz, A; Jiménez-Gómez, Y; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 6  Nº 7  2011  págs.  e22931
Autores: Valentí, Víctor; Martín, Marina; BEa; et al.
Revista: OBESITY SURGERY
ISSN 0960-8923  Vol. 21  Nº 9  2011  págs. 1438 - 1443
Background: Sleeve gastrectomy (SG) has been used for the surgical treatment of morbid obesity as a first or definitive procedure with satisfactory results. The objective of this study in rats was to establish the effects of SG on weight loss depending on the post-surgical type of diet followed. Methods: Thirty male Wistar rats were fed ad libitum during 3 months on a high-fat diet (HFD) to induce obesity. After this first phase, rats were subdivided in three groups of ten rats each and underwent a sham intervention, an SG, or no surgery but were pair-fed to the amount of food eaten by the animals of the SG group. At this time point, half of the animals in each group continued to be fed on the HFD, while the other half was switched to a normal chow diet (ND). Thus, the following subgroups were established: sham-ND, sleeve-ND, pair-fed-ND as well as sham-HFD, sleeve-HFD, and pair-fed-HFD. Body weight and food intake were recorded daily for 4 weeks. The feed efficiency rate (FER) was determined from weekly weight gains and caloric consumption during this period. Results: Statistically significant (P¿<¿0.05) differences in body weight were observed between the six experimental groups after 4 weeks of the interventions with rats in the sleeve-ND group experimenting the highest weight loss (-78.2¿±¿10.3 g) and animals in the pair-fed-HFD group exhibiting the lowest weight reduction (-4.0¿±¿0.1 g). Interestingly, the FER value of rats that underwent the SG and continued to be fed on a HFD was significantly (P¿<¿0.05) lower than that of sham operated and pair-fed animals on the same diet. Conclusion: The positive effects of SG on weight reduction are observed in obese rats submitted to the intervention and subsequently following an ND or even an HFD.
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
ISSN 0939-4753  Vol. 21  Nº 4  2011  págs. 245 - 253
Our work shows that NAMPT circulating concentrations and mRNA expression levels in PBC are increased in obese patients and that plasma NAMPT levels are related to inflammation, lipid metabolism and hepatic enzymes suggesting a potential involvement in fatty liver disease and in the obesity-associated inflammatory state.
Autores: Mendieta-Zeron, H.; Larrad-Jimenez, A.; Burrell, María Ángela; et al.
Revista: DIABETES & METABOLIC SYNDROME
ISSN 1878-0334  Vol. 5  Nº 2  2011  págs. 66 - 70
INTRODUCTION: Factors leading to weight loss and weight stabilization after bariatric surgery are not fully understood. Our aim was to evaluate, in Sprague-Dawley rats, the histological and gut hormonal changes after Larrad-biliopancreatic diversion (Larrad-BPD). MATERIALS AND METHODS: Rats randomly underwent the following protocols: Larrad-BPD (n=4) versus pair fed (PF) (n=4). Weight and food intake were measured every day. By immunohistochemistry ghrelin was examined in the stomach, while cholecystokinin (CCK), glucagon-like-peptide-1 (GLP-1), peptide YY (PYY) and serotonin (5-HT) expression were analyzed in alimentary limb and ileum following or not the Larrad-BPD. RESULTS: Larrad-BPD rats exhibited significant (P<0.05) weight loss compared to PF rats. Villi enlongation was observed in Larrad-BPD rats. In residual stomach, ghrelin was diminished. In the alimentary limb, ghrelin and CCK positive cells were detected more than in the ileum of PF rats. GLP-1 expression was decreased and PYY expression was absent after Larrad-BPD compared with PF rats. DISCUSSION: Larrad-BPD is followed by histological changes and a pleiotropic gut endocrine response aimed to compensate the reduction of intestinal area exposed to food. Until now, the hormones responsible for the intestinal hypertrophy have not been defined.
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: JOURNAL OF NUTRITIONAL BIOCHEMISTRY
ISSN 0955-2863  Vol. 22  Nº 7  2011  págs. 634 - 641
Autores: Salvador, Francisco Javier; Frühbeck, Gema;
Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
ISSN 1137-6627  Vol. 34  Nº 2  2011  págs. 141 - 144
Autores: Catalán, V; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
Revista: JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN 0021-972X  Vol. 96  Nº 1  2011  págs. 200 - 209
Autores: Rodríguez, Amaia; Catalán, V; Becerril, Sara; et al.
Revista: ADIPOBIOLOGY
ISSN 1313-3705  Vol. 2  2010  págs. 9 - 22
Aquaporins (AQPs) are water channels that facilitate a rapid transport of water, across cell membranes. In some cases, these pores are also permeated by small solutes, particularly glycerol. Thirteen aquaporins (AQP0-12) have been identified so far in mammalian tissues. The disruption of the genes encoding aquaporins in transgenic mice has revealed their implication in physiological and pathophysiological processes, including renal water absorption, neural function, digestion, tumour angiogenesis, and reproduction. A subset of aquaporins that transport both water and glycerol, the `aquaglyceroporins¿, regulate glycerol content in epidermal, fat and other tissues, and are involved in skin hydration, fat metabolism and gluconeogenesis. Better understanding of the exact mechanisms and regulation of aquaporins might be useful for designing potential drug targets against different metabolic disorders, such as stroke, glaucoma, brain ooedema, cancer, diabetes and obesity.
Autores: Fernandez-Real, JM.; Menendez, JA.; Moreno-Navarrete, JM.; et al.
Revista: DIABETES
ISSN 0012-1797  Vol. 59  Nº 6  2010  págs. 1506 - 11
Our results suggest that circulating FASN is a biomarker of overnutrition-induced insulin resistance that could provide diagnostic and prognostic advantages by providing insights on the individualized metabolic stress.
Autores: Ortega, FJ; Vázquez-Martín, A; Moreno-Navarrete, JM; et al.
Revista: INTERNATIONAL JOURNAL OF OBESITY
ISSN 0307-0565  Vol. 34  Nº 3  2010  págs. 487 - 499
Autores: Frühbeck, Gema;
Revista: OBESITY FACTS
ISSN 1662-4025  Vol. 3  Nº 4  2010  págs. 219 - 221
Autores: Rodríguez, Amaia; Gómez-Ambrosi, J; Catalán, V; et al.
Revista: Journal of hypertension
ISSN 0263-6352  Vol. 28  Nº 3  2010  págs. 560 - 567
Objective The gut-derived hormone, ghrelin, improves cardiac function in healthy individuals and patients with chronic heart failure. The aim of this study was to investigate whether the major isoforms of the hormone, acylated and desacyl ghrelin, are related to inappropriate left ventricular mass in patients with the metabolic syndrome (MetS). Methods and results Plasma concentrations of ghrelin forms were measured in 180 white participants (65 normal weight, 60 obese without MetS and 55 obese with MetS; 56% men). MetS was defined according to Adult Treatment Panel III criteria. The presence of left ventricular hypertrophy (LVH) was diagnosed by sex-specific left ventricular mass/height(2.7) cut-off values (> 49.2 g/m(2.7) for men and > 46.7 g/m(2.7) for women). Circulating concentrations of acylated ghrelin were increased in obesity and MetS, whereas desacyl ghrelin levels were decreased. Compared with participants in the lowest tertiles, the age-adjusted and sex-adjusted odds of having MetS were lower in the highest category of desacyl ghrelin (odds ratio 0.1, 95% confidence interval 0.1-0.4, P < 0.001). The prevalence of LVH was increased in the highest tertile of acylated ghrelin (odds ratio 3.4, 95% confidence interval 1.7-5.6, P < 0.05). Plasma acylated ghrelin was increased (P < 0.05) in patients with MetS exhibiting LVH compared with those with appropriate left ventricular mass, whereas plasma desacyl ghrelin was not changed (P = 0.490). Conclusion Acylated ghrelin was positively associated with SBP and left ventricular mass indices, even after correction for BMI. These results suggest that the increased acylated ghrelin concentrations may represent a compensatory mechanism to overcome the development of hypertension and LVH in patients with MetS.
Autores: Sáinz, Neira; Rodríguez, Amaia; Catalán, V; et al.
Revista: MEDIATORS OF INFLAMMATION
ISSN 0962-9351  Vol. 2010  2010  págs.  784343
Obese leptin-deficient ob/ob mice exhibit a low-grade chronic inflammation together with a low muscle mass. Our aim was to analyze the changes in muscle expression levels of genes related to oxidative stress and inflammatory responses in leptin deficiency and to identify the effect of in vivo leptin administration. Ob/ob mice were divided in three groups as follows: control ob/ob, leptin-treated ob/ob (1 mg/kg/d) and leptin pair-fed ob/ob mice. Gastrocnemius weight was lower in control ob/ob than in wild type mice (P < .01) exhibiting an increase after leptin treatment compared to control and pair-fed (P < .01) ob/ob animals. Thiobarbituric acid reactive substances, markers of oxidative stress, were higher in serum (P < .01) and gastrocnemius (P = .05) of control ob/ob than in wild type mice and were significantly decreased (P < .01) by leptin treatment. Leptin deficiency altered the expression of 1,546 genes, while leptin treatment modified the regulation of 1,127 genes with 86 of them being involved in oxidative stress, immune defense and inflammatory response. Leptin administration decreased the high expression of Crybb1, Hspb3, Hspb7, Mt4, Cat, Rbm9, Serpinc1 and Serpinb1a observed in control ob/ob mice, indicating that it improves inflammation and muscle loss
Autores: Poulain-Godefroy, O; Le Bacquer, O; Plancq, P; et al.
Revista: MEDIATORS OF INFLAMMATION
ISSN 0962-9351  Vol. 2010  2010  págs. 823486
Autores: Galofré, JC; Frühbeck, Gema; Salvador, Francisco Javier;
Revista: HOT THYROIDOLOGY
ISSN 2075-2202  Vol. 6  Nº 10  2010  págs. 1 - 22
Autores: Rodríguez, Amaia; Gómez-Ambrosi, J; Catalán, V; et al.
Revista: MEDIATORS OF INFLAMMATION
ISSN 0962-9351  Vol. 2010  2010  págs. 105489
Leptin blocks the proliferative response to Ang II through NO-dependent mechanisms. The attenuation of this inhibitory effect of leptin in spontaneous hypertension appears to be due to a reduced NO bioavailability in VSMCs
Autores: Gómez-Ambrosi, J; Catalán, V; Rodríguez, Amaia; et al.
Revista: JOURNAL OF NUTRITIONAL BIOCHEMISTRY
ISSN 0955-2863  Vol. 21  Nº 8  2010  págs. 774 - 780
Adipose tissue is highly vascularized implying that angiogenesis takes place in its expansion. The aim of this study was to compare the concentrations of members of the vascular endothelial growth factor (VEGF) family in obesity. Serum concentrations of VEGFs were analyzed in 15 lean (BMI 20.3+/-2.5 kg/m(2)) and 24 obese (BMI 47.6+/-5.9 kg/m(2)) volunteers. Obese patients showed significantly increased circulating VEGF-A (150+/-104 vs. 296+/-160 pg/ml; P&lt;.05), VEGF-B (2788+/-1038 vs. 4609+/-2202 arbitrary units; P&lt;.05) and VEGF-C (13 453+/-5750 vs. 17 635+/-5117 pg/ml; P&lt;.05) concentrations. Interestingly, levels of VEGF-D were reduced in obese individuals (538+/-301 vs. 270+/-122 pg/ml; P&lt;.01). In addition, VEGF-A significantly decreased after weight loss following Roux-en-Y gastric bypass (BMI from 46.0+/-8.0 to 28.9+/-4.2 kg/m(2)P&lt;.0001 vs. initial) from 345+/-229 to 290+/-216 pg/ml (P&lt;.01). Moreover, in order to corroborate the human findings VEGF-A levels were analyzed during the expansion of adipose tissue in two dynamic models of murine obesity. Serum VEGF-A was significantly increased after 12 weeks on a high-fat diet (43.3+/-9.0 vs. 29.7+/-9.1 pg/ml; P&lt;.01) or in ob/ob mice (52.2+/-18.0 vs. 29.2+/-7.7 pg/ml; P&lt;.01) and was normalized after leptin replacement in the latter (32.4+/-14.0 pg/ml; P&lt;.01 vs. untreated ob/ob). Our data indicates the involvement of these factors in the expansion of adipose tissue that takes place in obesity in relation to the need for increased vascularization, suggesting that manipulation of the VEGF system may represent a potential target for the pharmacological treatment of obesity.
Autores: Fernández-Real, JM; Valdés, S; Manco, M; et al.
Revista: DIABETES CARE
ISSN 0149-5992  Vol. 33  Nº 4  2010  págs. 847 - 853
Objective: Impaired lung function and innate immunity have both attracted growing interest as a potentially novel risk factor for glucose intolerance, insulin resistance, and type 2 diabetes. We aimed to evaluate whether surfactant protein D (SP-D), a lung-derived innate immune protein, was behind these associations. Research Design and Methods: Serum SP-D was evaluated in four different cohorts. The cross-sectional associations between SP-D and metabolic and inflammatory parameters were evaluated in two cohorts, the cross-sectional relationship with lung function in one cohort, and the longitudinal effects of weight loss on fasting and circadian rhythm of serum SP-D and cortisol concentrations in one prospective cohort. Results: In the cross-sectional studies, serum SP-D concentration was significantly decreased in subjects with obesity and type 2 diabetes (P = 0.005) and was negatively associated with fasting and postload serum glucose. SP-D was also associated with A1C, serum lipids, insulin sensitivity, inflammatory parameters, and plasma insulinase activity. Smoking subjects with normal glucose tolerance, but not smoking patients with type 2 diabetes, showed significantly higher serum SP-D concentration than nonsmokers. Serum SP-D concentration correlated positively with end-tidal carbon dioxide tension (r = 0.54, P = 0.034). In the longitudinal study, fasting serum SP-D concentration decreased significantly after weight loss (P = 0.02). Moreover, the main components of cortisol and SP-D rhythms became synchronous after weight loss. Conclusions: These findings suggest that lung innate immunity, as inferred from circulating SP-D concentrations, is at the cross-roads of inflammation, obesity, and insulin resistance.
Autores: Hurtado del Pozo, C; Calvo, RM; Vesperinas-García, G.; et al.
Revista: OBESITY
ISSN 1930-7381  Vol. 18  Nº 5  2010  págs. 897 - 903
Housekeeping genes frequently used in gene expression studies are highly regulated in human adipose tissue. To ensure a correct interpretation of results, it is critical to select appropriate reference genes. Subcutaneous (SC) and omental (OM) adipose tissue expression was analyzed from lean and obese subjects using whole genome complementary DNA (cDNA) microarrays to identify stably expressed genes and commercial TaqMan low density arrays (LDAs), with 16 common control genes. The best candidate gene from microarrays analysis was F-box and leucine-rich repeat protein-10 (FBXL10) (fold-change 10(-3) P < 0.01), an ubiquitous nucleolar protein evolutionarily conserved. Hypoxanthine phosphoribosyltransferase 1 (HPRT1) and importin 8 (IPO8), were the best reference genes among the 16 genes in the LDAs with coefficient of variation (CV) of 4.51 and 4.55%, respectively. However, when the LDAs data were further analyzed by the geNorm and NormFinder softwares, IPO8, a nuclear protein mediating import of proteins, was the first and the third better reference gene, respectively. IPO8 and FBXL10 were further validated by real-time PCR in additional OM and SC fat samples and primary cultured preadipocytes. According to their CV, IPO8 resulted more suitable than FBXL10 in both adipose tissue depots and SC preadipocytes, whereas FBXL10 performed better than IPO8 in OM cultured preadipocytes. Both genes expression levels did not change throughout adipogenesis. Thus, we provide clear evidence that IPO8 and FBXL10 are good candidates to use as reference genes in gene expression studies in human OM and SC adipose tissues as well as differentiated primary preadipocytes
Autores: Moreno-Navarrete, JM; Catalán, V; Ortega, F; et al.
Revista: NUTRITION AND METABOLISM
ISSN 1743-7075  Vol. 7  Nº 27  2010 
Autores: Becerril, Sara; Rodríguez, Amaia; Catalán, V; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 5  Nº 6  2010  págs. e10962
BACKGROUND: Leptin and nitric oxide (NO) on their own participate in the control of non-shivering thermogenesis. However, the functional interplay between both factors in this process has not been explored so far. Therefore, the aim of the present study was to analyze the impact of the absence of the inducible NO synthase (iNOS) gene in the regulation of energy balance in ob/ob mice. METHODS AND FINDINGS: Double knockout (DBKO) mice simultaneously lacking the ob and iNOS genes were generated, and the expression of molecules involved in the control of brown fat cell function was analyzed by real-time PCR, western-blot and immunohistochemistry. Twelve week-old DBKO mice exhibited reduced body weight (p<0.05), decreased amounts of total fat pads (p<0.05), lower food efficiency rates (p<0.05) and higher rectal temperature (p<0.05) than ob/ob mice. Ablation of iNOS also improved the carbohydrate and lipid metabolism of ob/ob mice. DBKO showed a marked reduction in the size of brown adipocytes compared to ob/ob mutants. In this sense, in comparison to ob/ob mice, DBKO rodents showed an increase in the expression of PR domain containing 16 (Prdm16), a transcriptional regulator of brown adipogenesis. Moreover, iNOS deletion enhanced the expression of mitochondria-related proteins, such as peroxisome proliferator-activated receptor gamma coactivator-1 alpha (Pgc-1alpha), sirtuin-1 (Sirt-1) and sirtuin-3 (Sirt-3). Accordingly, mitochondrial uncoupling proteins 1 and 3 (Ucp-1 and Ucp-3) were upregulated in brown adipose tissue (BAT) of DBKO mice as compared to ob/ob rodents. CONCLUSION: Ablation of iNOS improved the energy balance of ob/ob mice by decreasing food efficiency through an increase in thermogenesis. These effects may be mediated, in part, through the recovery of the BAT phenotype and brown fat cell function improvement.
Autores: Fernández-Real, JM; Menéndez, JA; Frühbeck, Gema; et al.
Revista: NUTRITION AND METABOLISM
ISSN 1743-7075  Vol. 7  2010  págs. 14
Autores: Fernández-Real, JM; Ortega, F; Gómez-Ambrosi, J; et al.
Revista: OSTEOPOROSIS INTERNATIONAL
ISSN 0937-941X  Vol. 21  Nº 12  2010  págs. 2101 - 2107
Autores: Sabater, M; Moreno-Navarrete, JM; Ortega, FJ; et al.
Revista: JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN 0021-972X  Vol. 95  Nº 10  2010  págs. 4720 - 4728
Autores: Moreno-Navarrete, JM; Martínez-Barricarte, R; Catalán, V; et al.
Revista: DIABETES
ISSN 0012-1797  Vol. 59  Nº 1  2010  págs. 200 - 209
Autores: Fernández-Real, JM; Catalán, V; Moreno-Navarrete, JM; et al.
Revista: NUTRITION AND METABOLISM
ISSN 1743-7075  Vol. 7  2010  págs. 20
Autores: Laguna, S; Príncipe, RM; Botella, S; et al.
Revista: AVANCES EN DIABETOLOGIA
ISSN 1134-3230  Vol. 26  Nº 3  2010  págs. 173 - 177
Autores: Rodríguez, Amaia; Leire; Frühbeck, Gema;
Libro:  Aquaporins in health and disease; new molecular targets for drug discovery
2015  págs. 105-126
Autores: Rodríguez, Amaia; Leire; Frühbeck, Gema;
Libro:  Autophagy: cancer, other pathologies, inflammation, immunity, infection, and aging.
Vol. 6- Regulation of autophagy and selective autophagy   2015  págs. 121- 131
Autores: Rodríguez, Amaia; Catalán, V; Frühbeck, Gema;
Libro:  Satiation, satiety and the control of food intake
2013  págs. 75-111
Autores: Salvador, Francisco Javier; Escalada, J; et al.
Libro:  Diabetes tipo 2 surgery
2010  págs. 117 - 124
Autores: Frühbeck, Gema;
Libro:  Obesity
2010  págs. 87 - 106
Autores: Frühbeck, Gema;
Libro:  Obesity
2010  págs. 87 - 106

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