Nuestros investigadores

Javier Salvador Rodríguez

Publicaciones científicas más recientes (desde 2010)

Autores: Gargallo, Javier; et al.
Revista: EXPERT OPINION ON PHARMACOTHERAPY
ISSN 1465-6566  Vol. 20  Nº 4  2019  págs. 367 - 371
Autores: Salvador, Francisco Javier, (Autor de correspondencia)
Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
ISSN 2530-0180  Vol. 66  Nº 5  2019  págs. 275 - 277
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: 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: Sanchez, M. ; Sanchez, E.; Hernandez, M.; et al.
Revista: NUTRIENTS
ISSN 2072-6643  Vol. 11  Nº 6  2019  págs. 1359
There is a close relationship between lifestyle behaviors and excess adiposity. Although body mass index (BMI) is the most used approach to estimate excess weight, other anthropometric indices have been developed to measure total body and abdominal adiposity. However, little is known about the impact of physical activity and adherence to a Mediterranean diet on these indices. Here we report the results of a cross-sectional study with 6672 middle-aged subjects with low to moderate cardiovascular risk from the Ilerda Vascular (ILERVAS) project. The participants' adherence to physical activity (International Physical Activity Questionnaire short form) and MedDiet (Mediterranean Diet Adherence Screener) was evaluated. Measures of total adiposity (BMI, Clinica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE), and Deurenberg's formula), central adiposity (waist and neck circumferences, conicity index, waist to height ratio, Bonora's equation, A body adiposity index, and body roundness index), and lean body mass (Hume formula) were assessed. Irrespective of sex, lower indices of physical activity were associated with higher values of total body fat and central adiposity. This result was constant regardless of the indices used to estimate adiposity. However, the association between MedDiet and obesity indices was much less marked and more dependent on sex than that observed for physical activity. Lean body mass was influenced by neither physical activity nor MedDiet adherence. No joint effect between physical activity and MedDiet to lower estimated total or central adiposity indices was shown. In conclusion, physical activity is related to lower obesity indices in a large cohort of middle-aged subjects. MedDiet showed a slight impact on estimated anthropometric indices, with no joint effect when considering both lifestyle variables. ClinTrials.gov Identifier: NCT03228459.
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: 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: 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: 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: 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: 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: 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: 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: Silva, Camilo, (Autor de correspondencia); Varo, N; et al.
Revista: ANNALES D ENDOCRINOLOGIE
ISSN 0003-4266  Vol. 79  Nº 2  2018  págs. 85 - 86
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: 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: 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: 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: 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: 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: Pérez-Pevida, Belén, (Autor de correspondencia); Varela, N.; et al.
Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
ISSN 1137-6627  Vol. 40  Nº 3  2017  págs. 413 - 420
Background. Achieving an adequate control of glycaemic and cardiovascular risk factors (CVRFs) is essential in patients with type 2 diabetes mellitus (T2DM). However, several studies have shown that the percentage of patients achieving these goals is scarce. We evaluated the degree of control of CVRFs target goals in T2DM patients who regularly attend a specialized diabetic clinic. Methods. We studied T2DM patients who attended the specialized Diabetic Unit at the Department of Endocrinology of Clinica Universidad de Navarra with a minimum follow-up of one year. Clinical characteristics, chronic complications and treatments were collected and patients were classified into groups according to the fulfilment of target glycated haemoglobin (HbA1c), LDL cholesterol and blood pressure (BP) levels, predefined according to the presence of different comorbidities and the duration of T2DM. Results. We analysed 137 patients (75% men) with T2DM, with an average age of 67 years and a 12.7 year duration of diabetes. During follow-up, 83.9% of the patients were within the individualized HbA1c target, 76.6% considering BP and 67.2% in terms of LDL-cholesterol. In addition, 68% had concomitantly the three main variables within the target. Conclusions. In our population of T2DM, HbA1c, LDL cholesterol and BP targets were achieved in a substantial proportion of patients (67-91%). Perhaps the intense and individualized care offered through a specialized diabetes unit may explain these results.
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: 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: 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: Silva, Camilo; et al.
Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
ISSN 1137-6627  Vol. 39  Nº 1  2016  págs. 23-33
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: 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: 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: 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: 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: 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: Pérez-Pevida, Belén; et al.
Revista: AVANCES EN DIABETOLOGIA
ISSN 1134-3230  Vol. 31  2015  págs. 35
Autores: Pérez-Pevida, Belén; Sancho, Lidia; Guillen Valderrama, E; et al.
Revista: DIABETOLOGIA
ISSN 0012-186X  Vol. 58  Nº Supl. 1  2015  págs. 342
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: 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: 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: Pascual, Eider; Aubá, María; et al.
Revista: ENDOCRINOLOGIA Y NUTRICION
ISSN 1575-0922  Vol. 61  Nº 7  2014  págs.  377-381
The presence of thyroid autoimmunity in women with TSH above the recommended values at the beginning of pregnancy is not associated to development of GD. However, GD prevalence was higher in these patients as compared to the Spanish general population, suggesting the need for closer monitoring in pregnant women with TSH levels ¿ 2.5 mU/mL.
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; Guillén-Grima, F; et al.
Revista: ENDOCRINE REVIEWS
ISSN 0163-769X  Vol. 35  Nº 3 Supl.  2014  págs. MON-0493
The relationship between metformin, thyroid function, and thyroid volume has been of interest to many investigators. A number of studies have consistently reported a TSH-lowering effect of metformin in hypothyroid patients. In addition, some previous reports found that metformin, alone or in combination with levothyroxine, shrank thyroid nodules in diabetic individuals with insulin resistance. Furthermore, other authors showed an anti-goitrogenic effect of metformin on subjects with type 2 diabetes (T2DM). Unfortunately, literature on the association between T2DM and thyroid volume is sparse. We designed a two-group retrospective study with euthyroid T2DM patients treated with metformin (Group A) or with other anti-diabetes agents (Group B). Examined were basal TSH (mU/mL), HbA1c (%), BMI (kg/m2), and thyroid nodule size (mm) assessed by sonography. The same examinations were repeated one year later. Exclusion criteria included the following conditions: type 1 diabetes, thyroid dysfunction, levothyroxine or antithyroid treatment, and corticoid therapy. Results from Groups A and B were compared using the Student¿s t and the Mann-Whitney U tests. A total of 63 nodules were analyzed. Group A included 31 nodules from 18 patients. Group B included 32 nodules from 15 patients. Groups A and B pre-TSH levels were 1.62± 1.19 and 2.06± 1.28, respectively; we found no statistically significant differences between them (p=0.164). Groups A and B post-TSH levels were 1.34± 0.87 and 1.99± 1.33, respectively; we observed a statistically significant difference between them (p=0.003). Groups A and B basal nodules mean size were 17.31± 9.97 and 12.45± 8.12, respectively. After one year of treatment, Groups A and B nodules mean size were 17.97± 10.31 and 12.90±7.92, respectively; we did not observe a statistically significant difference between them (p=0.961). We observed no statistically significant difference between Groups A and B in pre- and post-BMI, HbA1c, T2DM duration (data not shown). No patient in Group B was treated with glitazones. Conclusions: Thyroid nodule size in euthyroid patients with T2DM diabetes remained unchanged following treatment with metformin for one year despite changes in TSH levels. Nothing to Disclose: EP, GG, FG, BP, PA, JL, JE, JS, JCG - See more at: http://press.endocrine.org/doi/abs/10.1210/endo-meetings.2014.THPTA.3.MON-0493#sthash.Hod9WZQL.dpuf
Autores: Pérez-Pevida, Belén; Pascual, Eider; et al.
Revista: AVANCES EN DIABETOLOGIA
ISSN 1134-3230  Vol. 30  2014  págs. 61
Introducción: Se ha demostrado que la intervención intensiva sobre factores de riesgo cardiovascular (FRCV) en diabetes mellitus tipo 2 (DM2) reduce y retrasa la aparición de complicaciones micro y macrovasculares. Objetivos: Evaluar el grado de control de los FRCV en pacientes con DM2 que acuden con regularidad a consulta. Material y métodos: Pacientes con DM2 recogidos consecutivamente entre mayo-diciembre de 2013. Los datos estudiados son los de la consulta actual. Tiempo medio de atención/paciente 45 minutos con media de dos revisiones anuales, distribución geográfica nacional y seguimiento mediante telemedicina. Objetivos de hemoglobina glicosilada (HbA1c), perfil lipídico y presión arterial (PA) predefinidos según comorbilidades y años de evolución de DM2: HbA1c < 6,5% (Grupo 1: < 70 años, sin complicaciones y con un tiempo de evolución < 5 años) o < 7,5% (Grupo 2: resto +: MDRD < 60, cardiopatía isquémica (CI) inestable, neuropatía autonómica, arteriopatía periférica significativa, hipoglucemias severas asintomáticas o expectativa corta de vida). Perfil lipídico: HDL > 50 mg/dL (M) o > 40 mg/dL (H), triglicéridos < 150 mg/dL y LDL < 70 o < 100 mg/dL, según presencia o no de enfermedad CV (CI, enfermedad cerebrovascular, arteriopatía periférica, macroalbuminuria o microalbuminuria asociada a hipertensión o tabaquismo). Presión arterial < 140/90 mmHg. Resultados: Características de la población: 137 pacientes (75% hombres/25% mujeres), 67 años de edad media y 12,7 años de evolución de DM2. 12,4% fumadores activos. El 15% con medidas higiénico-dietéticas, 50% antidiabéticos orales (ADO), 35% insulina (54% con ADO, 46% con sólo insulina). Tratamiento antihipertensivo el 80% (15% calcioantagonista, 13% betabloqueante, 12% IECA, 27% ARAII y 33% combinación con diurético), hipolipemiante el 84,6% (72% estatinas/28% estatinas + ezetimibe) y antiagregante en 48%. Variables dentro del objetivo (tabla): Objetivo de HbA1c: 74,5%. PA: el 76,6% presentaba una cifra de PA < 140/90 mmHg. Objetivo de LDL: 67,2%; triglicéridos: 81,3%; colesterol No-HDL: 79%; HDL: 87%. El 68% con tres variables principales dentro del objetivo: HbA1c, PA y LDL colesterol. Función renal y albuminuria: 78% sin albuminuria con MDRD medio de 89 mL/min/1,73 m2, 12,5% microalbuminuria con MDRD medio de 84,3 y 9,5% macroalbuminuria con MDRD medio de 54,5. Dentro del objetivo Si No HbA1c Grupo 1: 8 (media = 5,7%) Grupo 1: 0 Grupo 2: 103 (media = 6,7%) Grupo 2: 26 (media = 8,9%) Presión arterial 105 32 Lípidos (LDL) < 70 mg/dL: 28 (media = 51 mg/dL) < 70 mg/dL: 27 (media = 88,7 mg/dL) < 100 mg/dL: 64 (media = 65,3 mg/dL) < 100 mg/dL: 18 (media = 123 mg/dL) Conclusiones: En nuestra población de DM2 la consecución de objetivos de HbA1c, perfil lipídico y PA se alcanzó en una importante proporción de pacientes (67-87%; media = 77,4%). Quizá la intensa e individualizada atención ofrecida puede explicar estos resultados.
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: Pérez-Pevida, Belén; Pascual, Eider; et al.
Revista: AVANCES EN DIABETOLOGIA
ISSN 1134-3230  Vol. 30  2014  págs. 64
Introducción: Estudios recientes ponen en duda la efectividad clínica y el coste-efectividad del autoanálisis de glucemia capilar (GC). Evaluamos la utilidad del autoanálisis de GC, para predecir la hemoglobina glicosilada (HbA1c) y detectar hipoglucemias, situación asociada a eventos cardiovasculares. Objetivos: Analizar la utilidad del autocontrol para predecir la cifra de HbA1c. Cuantificar la prevalencia de hipoglucemias en pacientes diabéticos tipo 1 y tipo 2 asociada a los distintos tipos de tratamientos antidiabéticos. Material y métodos: Descargas de glucómetros de pacientes en seguimiento en nuestra consulta. 1. Correlación entre GC y HbA1c. Se han estudiado 123 descargas de diabéticos tipo 1 con > 3.6 controles diarios, con pauta bolo-basal o ISCI. Se ha estudiado la GC media en el 1er, 2º, 3er mes y su asociación con la glucemia media estimada a través de la HbA1c (coeficiente de correlación de Pearson). 2. Detección de hipoglucemias. Se han estudiado 100 pacientes diabéticos tipo 1 y tipo 2, divididos según el tratamiento: antidiabéticos orales (ADO) no hipoglucemiantes e hipoglucemiantes o insulina (premezclada o pauta bolo-basal). Se han recogido de la historia clínica las hipoglucemias severas reportadas (HSR) en la consulta. Se ha estudiado la prevalencia de hipoglucemias según el tratamiento y la correlación con las HSR. Hemos realizado un estudio descriptivo y un estudio de regresión logística. Resultados: Relación entre GC y HbA1c. Observamos asociación positiva y significativa entre la GC media de las descargas y la glucemia media estimada a través de la HbA1c con un coeficiente de correlación de Pearson (r) de 0,588. Esta asociación es más fuerte entre la GC media del tercer mes y la HbA1c (r = 0,599). La media de GC (X) del tercer mes predice la cifra de HbA1c (Y): Y = 71,7 + 0,606 X. Estudio de hipoglucemias. El 4,5% de los diabéticos tipo1 han tenido algún episodio de HSR y según las descargas, el 41,5% ha tenido cifras < 50 mg/dL, 37% cifras 50-70 mg/dL y 21,5% ambas. Ningún diabético tipo 2 tuvo HSR, sin embargo, el 5,4% según el glucómetro ha tenido cifras < 50 mg/dL, en tratamiento con insulina ± ADO y 19,5% cifras de GC entre 51-70 mg/dl (11,7% con ADO no hipoglucemiante, 29% con ADO hipoglucemiante y 59,3% con insulina). Existe una asociación positiva y significativa entre las HSR y las hipoglucemias observadas según glucómetro (r = 0,531). Conclusiones: Nuestro estudio confirma la utilidad del autoanálisis en un doble sentido: como predictor de HbA1c en pacientes que realicen > 3,6 controles/día y para detectar un número importante de hipoglucemias, la mayoría asintomáticas, situación potencialmente relacionada con eventos cardiovasculares. Ambos pueden ayudar a mejorar el control glucémico en nuestros pacientes diabéticos.
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: Pascual, Eider; Pérez-Pevida, Belén; et al.
Revista: AVANCES EN DIABETOLOGIA
ISSN 1134-3230  Vol. 30  2014  págs. 4
Objetivos: La deficiencia de vitamina D es altamente prevalente en todo el mundo. Durante mucho tiempo ha sido conocida por ser una parte esencial del metabolismo óseo; sin embargo, la evidencia reciente sugiere una posible asociación entre los niveles disminuidos de vitamina D y diversas condiciones patológicas incluyendo las enfermedades cardiovasculares y la diabetes mellitus. Por ello, nuestro objetivo fue evaluar la asociación entre los niveles bajos de 25-hidroxivitamina D (25 (OH) D) y la presencia de trastornos cardiometabólicos en pacientes diabéticos tipo 2 (DM2). Material y métodos: Se realizó un estudio transversal en el que se incluyeron de forma aleatoria 108 pacientes con DM2 que realizaron cribado de los niveles de 25 (OH) D entre los años 2007 y 2013. Se excluyeron los pacientes diagnosticados de DM tipo 1, LADA o hiperparatiroidismo primario, aquellos en tratamiento con vitamina D y/o calcio, o con antecedente previo de cirugía bariátrica. Según los niveles de 25 (OH) D, los pacientes fueron divididos en tres grupos: deficiente (< 20 ng/ml), insuficiente (20- < 30 ng/ml) y normal (¿ 30 ng/ml). El análisis se realizó mediante Regresión Lineal Múltiple cuando la variable dependiente era cuantitativa y mediante Regresión Logística en el caso de variables categóricas. Resultados: Del total de la muestra, 69 (63,9%) pacientes presentaron niveles disminuidos de 25 (OH) D, entre ellos 36 (33,3%) deficiencia y 33 (30,6%) insuficiencia, y 39 (36,1%) obtuvieron valores normales. Niveles deficientes e insuficientes de 25 (OH) D fueron inversamente asociados con la cifra de hemoglobina glicosilada (A1c) (p = 0,006 y 0,012, respectivamente), la cardiopatía isquémica (p = 0,011 y 0,022), el infarto agudo de miocardio (p = 0,090 y 0,049) y la retinopatía diabética (p = 0,007 y 0,018), tras ajustar por edad, sexo, índice de masa corporal, hábito tabáquico y enólico, actividad física, estación del año, calcio, paratohormona, años de evolución de la diabetes, función renal y cociente albúmina/creatinina. Únicamente los niveles deficientes de 25 (OH) D obtuvieron una significativa asociación inversa con la glucemia basal (p = 0,008) y la vasculopatía periférica (p = 0,019). No se encontró asociación con las cifras de tensión arterial sistólica o diastólica, los niveles de colesterol total, HDL-colesterol, LDL-colesterol o triglicéridos, el accidente cerebrovascular, la neuropatía o la nefropatía diabética. Conclusiones: Niveles disminuidos de 25 (OH) vitamina D se asocian con un aumento del riesgo cardiovascular, peor control glucémico y mayor prevalencia de complicaciones derivadas de la DM2 en estos pacientes. Se requieren ensayos que permitan evaluar el impacto de la suplementación de la vitamina D sobre estos resultados para confirmar su causalidad.
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: 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: Jaques, F.; Rodriguez, S.; et al.
Revista: DIABETOLOGIA
ISSN 0012-186X  Vol. 56  Nº 4  2013  págs. 838 - 846
Cardiotrophin 1 (CT-1) is a recently described cytokine originally isolated from the heart where it has been shown to play an important role in apoptotic protection of cardiomyocytes and heart hypertrophy. Its beneficial properties have also been described in other organs such as liver and neuromuscular tissue. In the present study, we investigated whether CT-1 can confer protection against pro-apoptotic stimuli in pancreatic beta cells, and its role in insulin secretion and diabetes development. The effects of CT-1 on apoptosis and function were studied using MIN6B1 cells and freshly isolated murine pancreatic islets. The impact on the development of diabetes was evaluated in Ct1-null (Ct1 (-/-)) mice (the gene Ct1 is also known as Ctf1) using two streptozotocin (STZ)-induced models of diabetes. CT-1 has a protective effect in MIN6B1 cells and murine islets under the pro-apoptotic stimulus of serum deprivation, which correlates with the expression of B cell lymphoma-extra large, or following exposure to a mixture of cytokines. In addition, CT-1 enhances glucose-stimulated insulin secretion in MIN6B1 cells and this was repressed by inhibitors of phospholipase C. Furthermore, Ct1 (-/-) mice were more prone to develop diabetes, and their glucose tolerance test showed impaired plasma glucose clearance which correlated with decreased pancreatic insulin secretion. The results obtained from both in vitro and in vivo experiments show that CT-1 improves beta cell function and survival, and protects mice against STZ-induced diabetes.
Autores: Pascual, Eider; et al.
Revista: ENDOCRINOLOGIA Y NUTRICION
ISSN 1575-0922  Vol. 60  2013  págs. 91
Autores: Pascual, Eider; Pérez-Pevida, Belén; et al.
Revista: AVANCES EN DIABETOLOGIA
ISSN 1134-3230  Vol. 29  2013  págs. 38
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: 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; Gómez-Ambrosi, J; Catalán, V; et al.
Revista: Diabetologia
ISSN 0012-186X  Vol. 55  Nº 11  2012  págs. 3038 - 3050
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: 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: 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: Cervera-Paz FJ; Salvador, Francisco Javier; et al.
Revista: REVUE DE LARYNGOLOGIE - OTOLOGIE - RHINOLOGIE
ISSN 0035-1334  Vol. 132  Nº 3  2011  págs. 153-155.
The treatment of patients with idiopathic sudden sensorineural hearing loss must be performed as an emergency measure in order to prevent long term hearing deficit. Steroids in monotherapy provide the best outcome. There is some controversy regarding the most efficient route but in order to prevent side effects, intratympanic treatment is the preferred choice, especially in diabetic patients. We here present the case of a patient that developed hyperglycemia after systemic and intratympanic dexamethasone treatment for sudden hearing loss. We conclude that after intratympanic treatment great caution must be taken.
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: 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: Salvador, Francisco Javier; Escalada, J;
Revista: AVANCES EN DIABETOLOGIA
ISSN 1134-3230  Vol. 26  Nº 3  2010  págs. 151 - 155
Autores: Escalada, J; Salvador, Francisco Javier;
Revista: AVANCES EN DIABETOLOGIA
ISSN 1134-3230  Vol. 26  Nº 5  2010  págs. 370 - 372
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: Galofré, JC; Frühbeck, Gema; Salvador, Francisco Javier;
Revista: HOT THYROIDOLOGY
ISSN 2075-2202  Vol. 6  Nº 10  2010  págs. 1 - 22
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: Heber, D; Greenway, FL; Kaplan, LM; et al.
Revista: JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN 0021-972X  Vol. 95  Nº 11  2010  págs. 4823 - 4843
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: Laguna, S; Príncipe, RM; Botella, S; et al.
Revista: AVANCES EN DIABETOLOGIA
ISSN 1134-3230  Vol. 26  Nº 3  2010  págs. 173 - 177
Autores: Salvador, Francisco Javier; Aller, J; Fajardo, C; et al.
Revista: ENDOCRINOLOGIA Y NUTRICION
ISSN 1575-0922  Vol. 57  Nº Supl. 1  2010  págs. 13 - 23
Autores: Salvador, Francisco Javier; Escalada, J; et al.
Libro:  Diabetes tipo 2 surgery
2010  págs. 117 - 124
Autores: Galofre, Juan Carlos; Escalada, J; et al.
Libro:  La clínica y el laboratorio. Interpretación de análisis y pruebas funcionales. Exploración de los síndromes. Cuadro biológico de las enfermedades
2010  págs. 587 - 628