Nuestros investigadores

Pedro González Muniesa

Ciencias de la Alimentación y Fisiología
Facultad de Farmacia y Nutrición. Universidad de Navarra
Líneas de investigación
Relación entre la hipoxia y la obesidad en modelos celulares, animales y humanos, Relación entre la hipoxia y el transportador GLUT12 en modelos celulares y animales, Defensas antioxidantes, mitocondria y obesidad: en el tejido adiposo, Regulación de la ANGPTL4 (proteína relacionada con la angiogénesis) en el tejido adiposo, Sistema endocannabinoide, inflamación, angiogénesis y tejido adiposo, Metabolismo energético en células y animales: proteínas desacoplantes, Mediadores lipídicos bioactivos derivados de los ácidos grasos omega-3: potencial aplicación en obesidad, inflamación e insulino-resistencia., Sexenios CNEAI: 1 (2006, 2008-2012)
Índice H
16, (WoS, 27/10/2020)

Publicaciones científicas más recientes (desde 2010)

Autores: Graham, C. A. M., (Autor de correspondencia); Pedlar, C. R.; Hearne, G.; et al.
ISSN 2504-3161  Vol. 13  Nº 2  2020  págs. 99 - 106
Introduction: In the UK, the number of comorbidities seen in children has increased along with the worsening obesity rate. These comorbidities worsen into adulthood. Genome-wide association studies have highlighted single nucleotide polymorphisms associated with the weight status of adults and offspring individually. To date, in the UK, parental genetic, lifestyle, and social determinants of health have not been investigated alongside one another as influencers of offspring weight status. A comprehensive obesity prevention scheme would commence prior to conception and involve parental intervention including all known risk factors. This current study aims to identify the proportion of overweight that can be explained by known parental risk factors, including genetic, lifestyle, and social determinants of health with offspring weight status in the UK. Methods: A cross-sectional study was carried out on 123 parents. Parental and offspring anthropometric data and parental lifestyle and social determinants of health data were self-reported. Parental genetic data were collected by use of GeneFiX saliva collection vials and genotype were assessed for brain-derived neurotrophic factor (BDNF) gene rs6265, melanocortin 4 receptor (MC4R) gene rs17782313, transmembrane protein 18 (TMEM18) gene rs2867125, and serine/threonine-protein kinase (TNN13K) gene rs1514175. Associations were assessed between parental data and the weight status of offspring. Results: Maternal body mass index modestly predicted child weight status (p < 0.015; R-2 = 0.15). More mothers of overweight children carried the MC4R rs17782313 risk allele (77.8%; p = 0.007) compared to mothers of normal-weight children. Additionally, fathers who were not Caucasian and parents who slept for <7 h/night had a larger percentage of overweight children when compared to their counterparts (p = 0.039; p = 0.014, respectively). Conclusion: Associations exist between the weight status of offspring based solely on parental genetic, lifestyle, and social determinants of health data. Further research is required to appropriately address future interventions based on genetic and lifestyle risk groups on a pre-parent cohort.
Autores: Ovalle-Marin, A.; Reyes-Farias, M.; Vasquez, K. ; et al.
ISSN 1878-5093  Vol. 10  Nº 3  2020  págs. 531 - 545
BACKGROUND: Obesity occurs due to a positive energy imbalance, leading to the expansion of adipose tissue. This phenomenon triggers a chronic low-grade inflammatory state, which is associated with comorbidities development. It is, therefore, of great interest to investigate new counteracting nutritional strategies. In this regard, polyphenol-rich Chilean native fruits, Aristotelia chilensis (Maqui) and Berberis microphylla (Calafate), and also the non-Chilean Vaccinium corymbosum (Blueberry), have been associated with antioxidant and anti-inflammatory features. OBJECTIVE: To evaluate Maqui, Calafate, and Blueberry aqueous extracts treatments on the pathogenic response of human activated macrophages and visceral adipocytes. METHODS: THP-1 monocyte human cell line and differentiated human visceral preadipocytes were activated (with lipopolysaccharide and TNF-a, for 48 and 24 h, respectively), and treated with the aqueous extracts. Inflammation and oxidative stress markers were assessed. RESULTS: Lower NO and IL-6 secretion, and inhibited apoptosis in activated macrophages, were observed. Also, decreased gene expression of MCP-1 and secretion of IL-6, inhibited apoptosis, and increased levels of GSH in activated adipocytes were detected. CONCLUSIONS: Maqui, Calafate, and Blueberry extracts showed anti-inflammatory and antioxidant responses in human macrophages and adipocytes.
Autores: Banaszczak, M.; Maciejewska, D.; Drozd, A.; et al.
ISSN 1010-660X  Vol. 56  Nº 2  2020  págs. 58
Background: It was previously shown that a bodyweight reduction among patients with nonalcoholic fatty liver (NAFLD) was connected to the lower concentration of arachidonic and linoleic acid derivatives in their blood. We hypothesized that the concentration of these lipids was correlated with the extent of their body mass reduction and, thus, liver steatosis. Methods: We analyzed 68 individuals who completed the dietary intervention. Patients were divided into two groups depending on their body mass reduction (more or less than 7%). Before and after the dietary intervention, all patients had the following measurements recorded: body mass, waist circumference, stage of steatosis, fatty liver index, liver enzymes, lipid parameters, insulin and glucose. Concentrations of lipoxins A4 (LTX A4), hydroxyeicosatetraenoic fatty acids (5(S)-HETE, 12(S)-HETE and 16(S)-HETE), hydroxyoctadecaenoic acids (9(S)-HODE and 13(S)-HODE) and 5-oxo-eicosatetraenoic acid (5-oxo-ETE) were measured in serum samples collected before and after the dietetic intervention using high-performance liquid chromatography (HPLC). Results: Patients who reduced their body mass by more than 7% revealed a significant improvement in their steatosis stage, waist circumference, fatty liver index, triglycerides and cholesterol. Conclusion: A reduction in body mass by more than 7% but not by less than 7% revealed a significant improvement in steatosis stage; waist circumference; fatty liver index; and levels of triglycerides, cholesterol, 5-oxo-ETE and LTXA-4.
Autores: Lopez-Pascual, A. ; Urrutia-Sarratea, A. ; Lorente Cebrián, Silvia; et al.
ISSN 1942-0900  Vol. 2019  2019  págs. 2695289
Insulin resistance is associated with oxidative stress, mitochondrial dysfunction, and a chronic low-grade inflammatory status. In this sense, cerium oxide nanoparticles (CeO2 NPs) are promising nanomaterials with antioxidant and anti-inflammatory properties. Thus, we aimed to evaluate the effect of CeO, NPs in mouse 3T3-L1 adipocytes, RAW 264.7 macrophages, and C2C12 myotubes under control or proinflammatory conditions. Macrophages were treated with LPS, and both adipocytes and myotubes with conditioned medium (25% LPS-activated macrophages medium) to promote inflammation. CeO2 NPs showed a mean size of <= 25.3 nm (96.7%) and a zeta potential of 30.57 +/- 0.58 mV, suitable for cell internalization. CeO, NPs reduced extracellular reactive oxygen species (ROS) in adipocytes with inflammation while increased in myotubes with control medium. The CeO2 NPs increased mitochondrial content was observed in adipocytes under proinflammatory conditions. Furthermore, the expression of Adipoq and Il10 increased in adipocytes treated with CeO, NPs. In myotubes, both Il1b and Adipoq were downregulated while Irs1 was upregulated. Overall, our results suggest that CeO2 NPs could potentially have an insulin-sensitizing effect specifically on adipose tissue and skeletal muscle. However, further research is needed to confirm these findings.
Autores: Norouzirad, R. ; Gholami, H. ; Ghanbari, M.; et al.
ISSN 0024-3205  Vol. 230  2019  págs. 188 - 196
Aims: Hyperoxia has beneficial metabolic effects in type 2 diabetes. However, hyperoxia exacerbates already existing oxidative stress in type 2 diabetes. Nitrate, a nitric oxide donor, is an effective new treatment in type 2 diabetes and also has antioxidant properties. The aim of this study was to determine whether nitrate administration can attenuate hyperoxia-induced oxidative stress in obese type 2 diabetic rats. Main methods: Fifty-six male Wistar rats (190-210 g) were divided into 8 groups: Controls (non-treated, nitratetreated, O-2-treated, and nitrate + O-2-treated) and diabetes (non-treated, nitrate-treated, O-2-treated, and nitrate + O-2-treated). Diabetes was induced using high-fat diet and low-dose of streptozotocin (30 mg/kg). Rats in intervention groups, were exposed to 95% oxygen and consumed sodium nitrate (100 mg/L) in drinking water. Serum fasting glucose, oxidized (GSSG) and reduced (GSH) glutathiones, total oxidant status (TOS), catalase and superoxide dismutase (SOD) activities, and total antioxidant capacity (TAC) were measured after intervention. Oxidative stress index (OSI) was calculated as TOS/TAC ratio. Key findings: Diabetic rats had increased oxidative stress and hyperoxia exacerbated it. In 0 2 -diabetic rats, nitrate decreased GSSG (102.7 +/- 2.1 vs. 236.0 +/- 20.1 mu M, P < 0.001), TOS (67.7 +/- 7.3 vs. 104 +/- 3.8 mu M, P < 0.001), and OSI (0.44 +/- 0.04 vs. 0.91 +/- 0.07, P < 0.001) and increased catalase (2.8 +/- 0.13 vs. 1.8 +/- 0.21 KU/L, P = 0.014), SOD (53.4 +/- 1.5 vs. 38.4 +/- 1.2 U/mL, P < 0.001), GSH (43.7 +/- 1.4 vs. 17.8 +/- 0.5 mM, P = 0.003), TAC (152.5 +/- 1.9 vs. 116.7 +/- 5.0 mM, P < 0.001), and GSH/GSSG ratio (0.43 +/- 0.01 vs. 0.08 +/- 0.01, P = 0.005). Nitrate also potentiated effects of hyperoxia on decreasing fasting glucose. Significance: Our results showed that dietary nitrate attenuates hyperoxia-induced oxidative stress in type 2 diabetic rats.
Autores: Martínez Fernández, Leyre; González Muniesa, Pedro; Sáinz Amillo, Neira; et al.
ISSN 1613-4133  Vol. 63  Nº 24  2019  págs. 1 - 9
SCOPE: To study the effects of Maresin 1 (MaR1), a docosahexaenoic-acid-derived lipid mediator, on fibroblast growth factor 21 (FGF21) production and to characterize the tissue-specific regulation of Fgf21 and its signaling pathway in liver, skeletal muscle, and white adipose tissue (WAT). METHODS AND RESULTS: Diet-induced obese (DIO) mice are treated with MaR1 (50g kg-1 , 10 days, oral gavage) and serum FGF21 levels and liver, muscle and WAT Fgf21, beta-Klotho, Fgfr1, Egr1, and cFos mRNA expression are evaluated. Additionally, MaR1 effects are tested in mouse primary hepatocytes, HepG2 human hepatocytes, C2C12 myotubes, and 3T3-L1 adipocytes. In DIO mice, MaR1 decreases circulating FGF21 levels and HFD-induced hepatic Fgf21 mRNA expression. MaR1 increases hepatic beta-Klotho, Egr1, and cFos in DIO mice. In WAT, MaR1 counteracts the HFD-induced downregulation of Fgf21, Fgfr1, and beta-Klotho. In muscle, MaR1 does not modify Fgf21 but promoted Fgfr1 expression. In mouse primary hepatocytes, MaR1 decreases Fgf21 expression and downregulated Pparalpha mRNA levels. In HepG2 cells, MaR1 reverses the increased production of FGF21 and the downregulation of FGFR1, Beta-KLOTHO, EGR1, and cFOS induced by palmitate. Preincubation with a PPARalpha antagonist prevents MaR1 effects on FGF21 secretion. CONCLUSION: The ability of MaR1 to modulate FGF21 can contribute to its beneficial metabolic effects.
Autores: Graham, C. A. M.; Pipe, J. ; Holton, J. ; et al.
ISSN 0029-6651  Vol. 78  Nº OCE1  2019  págs. E2 - E2
Autores: Martinez-Hernandez, L.; González Muniesa, Pedro; Sáinz Amillo, Neira; et al.
ISSN 0250-6807  Vol. 75  2019  págs. 23
Autores: Crujeiras Martínez, Ana Belén; Cordero Sánchez, Paul; García Díaz, Diego Fernando; et al.
ISSN 1942-0900  2019 
Autores: Yang, J. C. Z.; Fernández Galilea, Marta; Martínez Fernández, Leyre; et al.
ISSN 2072-6643  Vol. 11  Nº 4  2019 
Aging is a complex phenomenon characterized by the progressive loss of tissue and organ function. The oxidative-stress theory of aging postulates that age-associated functional losses are due to the accumulation of ROS-induced damage. Liver function impairment and non-alcoholic fatty liver disease (NAFLD) are common among the elderly. NAFLD can progress to non-alcoholic steatohepatitis (NASH) and evolve to hepatic cirrhosis or hepatic carcinoma. Oxidative stress, lipotoxicity, and inflammation play a key role in the progression of NAFLD. A growing body of evidence supports the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFA), mainly docosahaexenoic (DHA) and eicosapentaenoic acid (EPA), on metabolic diseases based on their antioxidant and anti-inflammatory properties. Here, we performed a systematic review of clinical trials analyzing the efficacy of n-3 PUFA on both systemic oxidative stress and on NAFLD/NASH features in adults. As a matter of fact, it remains controversial whether n-3 PUFA are effective to counteract oxidative stress. On the other hand, data suggest that n-3 PUFA supplementation may be effective in the early stages of NAFLD, but not in patients with more severe NAFLD or NASH. Future perspectives and relevant aspects that should be considered when planning new randomized controlled trials are also discussed.
Autores: Lorente Cebrián, Silvia (Autor de correspondencia); González Muniesa, Pedro; Milagro Yoldi, Fermín Ignacio; et al.
ISSN 0143-5221  Vol. 133  Nº 1  2019  págs. 23 - 40
Obesity is a metabolic condition usually accompanied by insulin resistance (IR), type 2 diabetes (T2D), and dyslipidaemia, which is characterised by excessive fat accumulation and related to white adipose tissue (WAT) dysfunction. Enlargement of WAT is associated with a transcriptional alteration of coding and non-coding RNAs (ncRNAs). For many years, big efforts have focused on understanding protein-coding RNAs and their involvement in the regulation of adipocyte physiology and subsequent role in obesity. However, diverse findings have suggested that a dysfunctional adipocyte phenotype in obesity might be also dependent on specific alterations in the expression pattern of ncRNAs, such as miRNAs. The aim of this review is to update current knowledge on the physiological roles of miRNAs and other ncRNAs in adipose tissue function and their potential impact on obesity. Therefore, we examined their regulatory role on specific WAT features: adipogenesis, adipokine secretion, inflammation, glucose metabolism, lipolysis, lipogenesis, hypoxia and WAT browning. MiRNAs can be released to body fluids and can be transported (free or inside microvesicles) to other organs, where they might trigger metabolic effects in distant tissues, thus opening new possibilities to a potential use of miRNAs as biomarkers for diagnosis, prognosis, and personalisation of obesity treatment. Understanding the role of miRNAs also opens the possibility of using these molecules on individualised dietary strategies for precision weight management. MiRNAs should be envisaged as a future therapeutic approach given that miRNA levels could be modulated by synthetic molecules (f.i. miRNA mimics and inhibitors) and/or specific nutrients or bioactive compounds.
Autores: Lopez Pascual, Amaya; Arévalo, Jessica; Martínez Hernández, Alfredo; et al.
ISSN 1664-2392  Vol. 9  2018 
Background: Metabolic syndrome (MetS) is characterized by the clustering of hyperglycemia, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol levels and central adiposity. Altitude has been proposed as a protective factor to prevent the development of MetS and its components. Aim: To determine whether living at geographical elevation is associated with MetS and its individual components after adjustment for potential confounders in an Ecuadoran population. Methods: The study included 260 Ecuadoran university graduates over 20 years of age, from the coastal or the Andean Altiplano region. The altitude of residence was imputed with the postal code of each participant residence according to the data of the Ecuadoran Geophysical Institute of the National Polytechnic School. MetS was defined according to the harmonizing definition. Logistic regression models were fitted to assess the relationship between altitude level and the prevalence of MetS and its individual components. To test the internal validity, re-sampling techniques were used (1,000 bootstrap samples). Results: Living at high altitude was associated with less hypercholesterolemia (OR = 0.24; p < 0.001), hyperglycemia (OR = 0.25; p < 0.05) and MetS (OR = 0.24; p < 0.05), after adjusting for potential confounders. At high altitude the bootstrapped logistic regressionmodels showed lower prevalence of hypercholesterolemia (OR = 0.30; p < 0.05), hyperglycemia (OR = 0.22; p < 0.001) and MetS (OR = 0.28; p < 0.05). The MetS score (0-5 points) showed a reduction in the number of MetS components at high altitude compared to sea level (B = -0.34; p = 0.002). A statistically significant lower self-reported energy intake was found in high altitude compared to sea level after adjustment for potential confounders (p < 0.001). Conclusion: In the present study concerning a small Ecuadoran population composed of highly educated adults living at the coast and the Andean Altiplano, living at high altitude (2,758-2,787m) was associated with a lower prevalence of MetS, hypercholesterolemia and hyperglycemia, compared to the participants at sea level (4-6m). In addition, an inverse association between altitude and self-reported energy intake was found after adjusting for covariates, suggesting a physiological role of appetite at high altitude even in acclimated subjects.
Autores: Lopez-Pascual, A. ; Lorente Cebrián, Silvia; Moreno Aliaga, María Jesús; et al.
ISSN 0021-9541  Vol. 234  Nº 1  2018  págs. 550 - 560
Obesity is a multifactorial, chronic, inflammatory disease that involves different processes, such as adipose tissue hypoxia. The aim of the current study was to characterize the effects of conditioned medium (CM) from lipopolysaccharide (LPS)-activated macrophages on the regulation of hypoxia-inducible factor 1 alpha (HIF-1 alpha)-related genes in murine adipocytes. For the in vitro analyses, 3T3-L1 murine adipocytes (9 days postdifferentiation) were incubated either in CM (25% medium of RAW 264.7 murine macrophages with 24hr 500ng/ml LPS), LPS at 500ng/ml, or hypoxia (Hx; 1% O-2, 94% N-2, 5% CO2) for 24hr. For the in vivo experiments, mice were fed a high-fat diet. Both epididymal white adipose tissue (eWAT) and adipocytes in CM showed upregulation of Glut1, Mcp1, Il10, Tnf, and Il1b. The secretion of IL-6, TNF-alpha, and MCP-1 was also increased in CM-treated adipocytes. Moreover, increased levels of HIF-1 alpha subunit and nuclear factor kappa B p65 were found after CM treatment, linking Hx, and inflammation. HIF-1 alpha directly bound vascular endothelial growth factor A (Vegfa) and uncoupling protein 2 (Ucp2) genes, up- and downregulating its expression, respectively. Furthermore, the oxygen consumption rate was 30% lower in CM. The siRNA knockdown of mammalian target of rapamycin (Mtor) reversed the induction of HIF-1 alpha found in CM. The macrophage infiltration simulated through CM seems to be a similar environment to an abnormally enlarged eWAT. We have evidenced that HIF-1 alpha plays a regulatory role in the expression of Vegfa and Ucp2 in CM. Finally, the inhibition of the mTOR pathway prevented the HIF-1 alpha activation induced by CM. The involvement of HIF-1 alpha under proinflammatory conditions provides insight into the origins of Hx in obesity.
Autores: Martínez-Fernández, L.; González Muniesa, Pedro; Laiglesia González, Laura María; et al.
ISSN 0892-6638  Vol. 31  Nº 5  2017  págs. 2135 - 2145
The beneficial actions of n-3 fatty acids on obesity-induced insulin resistance and inflammation have been related to the synthesis of specializedproresolving lipid mediators (SPMs) like resolvins.The aimof this study was to evaluate the ability of one of these SPMs, maresin 1 (MaR1), to reverse adipose tissue inflammation and/or insulin resistance in twomodels of obesity: diet-induced obese (DIO)mice and genetic (ob/ob) obesemice. In DIO mice, MaR1 (2 mg/kg; 10 d) reduced F4/80-positive cells and expression of the proinflammatory M1 macrophage phenotype marker Cd11c in white adipose tissue (WAT). Moreover, MaR1 decreased Mcp-1, Tnf-a, and Il-1b expression, upregulated adiponectin and Glut-4, and increasedAkt phosphorylation inWAT.MaR1 administration (2 mg/kg; 20 d) to ob/ob mice did not modify macrophage recruitment but increased the M2 macrophage markers Cd163 and Il-10.MaR1 reduced Mcp-1, Tnf-a, Il-1b, andDpp-4 and increased adiponectin gene expression inWAT. MaR1treatment also improved the insulin tolerance test of ob/ob mice and increased Akt andAMPKphosphorylation in WAT. These data suggest that treatment with MaR1 can counteract the dysfunctional inflamed WAT and could be useful to improve insulin sensitivity in murine models of obesity.
Autores: Lopez-Pascual, A.; Bes Rastrollo, Maira; Sayon Orea, María del Carmen; et al.
ISSN 1664-042X  Vol. 7  2017  págs. 658
Living in a geographically higher altitude affects oxygen availability. The possible connection between environmental factors and the development of metabolic syndrome (MetS) feature is not fully understood, being the available epidemiological evidence still very limited. The aim of the present study was to evaluate the longitudinal association between altitude and incidence of MetS and each of its components in a prospective Spanish cohort, The Seguimiento Universidad de Navarra (SUN) project. Our study included 6860 highly educated subjects (university graduates) free from any MetS criteria at baseline. The altitude of residence was imputed with the postal code of each individual subject residence according to the data of the Spanish National Cartographic Institute and participants were categorized into tertiles. MetS was defined according to the harmonized definition. Cox proportional hazards models were used to assess the association between the altitude of residence and the risk of MetS during follow-up. After a median follow-up period of 10 years, 462 incident cases of MetS were identified. When adjusting for potential confounders, subjects in the highest category of altitude (>456 m) exhibited a significantly lower risk of developing MetS compared to those in the lowest tertile (<122 m) of altitude of residence [Model 2: Hazard ratio = 0.75 (95% Confidence interval: 0.580.97); p for trend = 0.029]. Living at geographically higher altitude was associated with a lower risk of developing MetS in the SUN project. Our findings suggest that geographical elevation may be an important factor linked to metabolic diseases.
Autores: Lopez-Pascual, A.; Lasa, A.; Portillo, M. P.; et al.
ISSN 0250-6807  Vol. 71  Nº 1-2  2017  págs. 16 - 25
BACKGROUND: Deoxyribonucleic acid (DNA) methylation is an epigenetic modification involved in gene expression regulation, usually via gene silencing, which contributes to the risks of many multifactorial diseases. The aim of the present study was to analyze the influence of resting oxygen consumption on global and gene DNA methylation as well as protein secretion of inflammatory markers in blood cells from obese subjects with sleep apnea-hypopnea syndrome (SAHS). METHODS: A total of 44 obese participants with SAHS were categorized in 2 groups according to their resting oxygen consumption. DNA methylation levels were evaluated using a methylation-sensitive high resolution melting approach. RESULTS: The analyzed interleukin 6 (IL6) gene cytosine phosphate guanine (CpG) islands showed a hypomethylation, while serum IL-6 was higher in the low compared to the high oxygen consumption group (p < 0.05). Moreover, an age-related loss of DNA methylation of tumor necrosis factor (B = -0.82, 95% CI -1.33 to -0.30) and long interspersed nucleotide element 1 (B = -0.46; 95% CI -0.87 to -0.04) gene CpGs were found. Finally, studied CpG methylation levels of serpin peptidase inhibitor, clade E member 1 (r = 0.43; p = 0.01), and IL6 (r = 0.41; p = 0.02) were positively associated with fat-free mass. CONCLUSIONS: These findings suggest a potential role of oxygen in the regulation of inflammatory genes. Oxygen consumption measurement at rest could be proposed as a clinical biomarker of metabolic health.
Autores: González Muniesa, Pedro; Martínez González, Miguel Ángel; Hu, F. B.; et al.
Título: Obesity
ISSN 2056-676X  Vol. 3  2017  págs. Article number: 17034
Excessive fat deposition in obesity has a multifactorial aetiology, but is widely considered the result of disequilibrium between energy intake and expenditure. Despite specific public health policies and individual treatment efforts to combat the obesity epidemic, >2 billion people worldwide are overweight or obese. The central nervous system circuitry, fuel turnover and metabolism as well as adipose tissue homeostasis are important to comprehend excessive weight gain and associated comorbidities. Obesity has a profound impact on quality of life, even in seemingly healthy individuals. Diet, physical activity or exercise and lifestyle changes are the cornerstones of obesity treatment, but medical treatment and bariatric surgery are becoming important. Family history, food environment, cultural preferences, adverse reactions to food, perinatal nutrition, previous or current diseases and physical activity patterns are relevant aspects for the health care professional to consider when treating the individual with obesity. Clinicians and other health care professionals are often ill-equipped to address the important environmental and socioeconomic drivers of the current obesity epidemic. Finally, understanding the epigenetic and genetic factors as well as metabolic pathways that take advantage of 'omics' technologies could play a very relevant part in combating obesity within a precision approach.
Autores: Norouzirad, R.; González Muniesa, Pedro; Ghasemi, A.;
ISSN 1942-0900  2017  págs. 5350267
The prevalence of obesity and diabetes is increasing worldwide. Obesity and diabetes are associated with oxidative stress, inflammation, endothelial dysfunction, insulin resistance, and glucose intolerance. Obesity, a chronic hypoxic state that is associated with decreased nitric oxide (NO) bioavailability, is one of the main causes of type 2 diabetes. The hypoxia-inducible factor-1 alpha (HIF-1 alpha) is involved in the regulation of several genes of the metabolic pathways including proinflammatory adipokines, endothelial NO synthase (eNOS), and insulin signaling components. It seems that adipose tissue hypoxia and NO-dependent vascular and cellular dysfunctions are responsible for other consequences linked to obesity-related disorders. Although hyperoxia could reverse hypoxic-related disorders, it increases the production of reactive oxygen species (ROS) and decreases the production of NO. Nitrate can restore NO depletion and has antioxidant properties, and recent data support the beneficial effects of nitrate therapy in obesity and diabetes. Although it seems reasonable to combine hyperoxia and nitrate treatments for managing obesity/diabetes, the combined effects have not been investigated yet. This review discusses some aspects of tissue oxygenation and the potential effects of hyperoxia and nitrate interventions on obesity/diabetes management. It can be proposed that concomitant use of hyperoxia and nitrate is justified for managing obesity and diabetes.
Autores: Díaz-Gutiérrez, J.; Martínez González, Miguel Ángel; Pons Izquierdo, Juan José; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 11  Nº 11  2016  págs. e0164483
BACKGROUND: Residence at high altitude has been associated with lower obesity rates probably due to hypoxia conditions. However, there is no evidence of this association in a free-living population. OBJECTIVES: We assessed the association between the altitude where each participant of a Spanish cohort (the SUN Project) was living and the incidence of overweight/obesity. METHODS: The SUN Project is a dynamic, prospective, multipurpose cohort of Spanish university graduates with a retention rate of 89%. We included in the analysis 9 365 participants free of overweight/obesity at baseline. At the baseline questionnaire, participants reported their postal code and the time they had been living in their city/village. We imputed the altitude of each postal code according to the data of the Spanish National Cartographic Institute and categorized participants in tertiles. We used Cox regression models to adjust for potential confounding variables. RESULTS: During a median follow-up of 10 years, we identified 2 156 incident cases of overweight/obesity. After adjusting for sex, age, time of residence at current city, baseline body mass index, physical activity, sedentarism and years of education (¿ 3 years, ¿ 4 years, Master/PhD), those participants in the third tertile (>456 m) exhibited a statistically significant 14% reduction in the risk of developing overweight/obesity in comparison to those in the first tertile (<124 m) (adjusted HR = 0.86; 95% CI: 0.77, 0.96). CONCLUSIONS: Living in cities of higher altitude was inversely associated with the risk of developing overweight/obesity in a cohort of Spanish university graduates.
Autores: Marinoni, M.; Cordero Sánchez, Paul; Martínez Hernández, Alfredo; et al.
ISSN 2380-548X  Vol. 2  Nº 1  2016  págs. 1 - 4
Abstract Obesity is now considered to be a global epidemic, impacting a great number of women and leading to a higher risk of obstetrical and gestational complications. One of such possible adverse outcomes in gestating female is placental hypoxia, which has been related to vascular remodeling and hypertension, as well as adaptive phenomena to reduce levels of oxidative stress and damage. A pool of female Sprague Dawley rats (n=63) was first assigned into two dietary groups (Control and High Sugar). Following mating, the pregnant rats (n=39) were again distributed into two oxygen treatment groups (Normoxia and Hypoxia) for 3 weeks, and tissue sampling and biochemical analyses were carried out. The main results of this study are the following: 1) Hypoxia during gestation may lead to a reduction in the average number of pups per mother, 2) Hypoxia during gestation treatment may lead to a decrease in maternal serum TG levels, and consequentially 3) Hypoxia during gestation may lead to a reduction in TyG Index levels. These results suggest that hypoxia could generate a beneficial response in pregnant Sprague Dawley rats to salvage both maternal and fetal viability. Thus, reproducing mild hypoxic conditions could result being a viable therapeutic option in preventing gestational adversities. In conclusion, progress was made in recognizing the possible role of a mild hypoxic environment in stimulating a maternal protective response.
Autores: González Muniesa, Pedro; López-Pascual, A.; De-Andrés, J.; et al.
ISSN 1138-7548  Vol. 71  Nº 3  2015  págs. 589 - 599
Strategies designed to reduce adiposity and cardiovascular-accompanying manifestations have been based on nutritional interventions conjointly with physical activity programs. The aim of this 13-week study was to investigate the putative benefits associated to hypoxia plus exercise on weight loss and relevant metabolic and cardiorespiratory variables, when prescribed to obese subjects with sleep apnea syndrome following dietary advice. The participants were randomly distributed in the following three groups: control, normoxia, and hypoxia. All the subjects received dietary advice while, additionally, normoxia group was trained under normal oxygen concentration and Hypoxia group under hypoxic conditions. There was a statistically significant decrease in fat-free mass (Kg) and water (%) on the control compared to normoxia group (p¿<¿0.05 and p¿<¿0.01, respectively). Body weight, body mass index, and waist circumference decreased in all the groups after the study. Moreover, leukocyte count was increased after the intervention in hypoxia compared to control group (p¿<¿0.05). There were no statistically significant variations within groups in other variables, although changes in appetite were found after the 13-week period. In addition, associations between the variations in the leukocyte count and fat mass have been found. The hypoxia group showed some specific benefits concerning appetite and cardiometabolic-related measurements as exertion time and diastolic blood pressure, with a therapeutical potential.
Autores: Rendo Urteaga, Tara; García Calzón, Sonia; González Muniesa, Pedro; et al.
ISSN 0007-1145  Vol. 113  Nº 2  2015  págs. 331 - 342
The present study analyses the gene expression profile of peripheral blood mononuclear cells (PBMC) from obese boys. The aims of the present study were to identify baseline differences between low responders (LR) and high responders (HR) after 10 weeks of a moderate energy-restricted dietary intervention, and to compare the gene expression profile between the baseline and the endpoint of the nutritional intervention. Spanish obese boys (age 10-14 years) were advised to follow a 10-week moderate energy-restricted diet. Participants were classified into two groups based on the association between the response to the nutritional intervention and the changes in BMI standard deviation score (BMI-SDS): HR group (n 6), who had a more decreased BMI-SDS; LR group (n 6), who either maintained or had an even increased BMI-SDS. The expression of 28 869 genes was analysed in PBMC from both groups at baseline and after the nutritional intervention, using the Affymetrix Human Gene 1.1 ST 24-Array plate microarray. At baseline, the HR group showed a lower expression of inflammation and immune response-related pathways, which suggests that the LR group could have a more developed pro-inflammatory phenotype. Concomitantly, LEPR and SIRPB1 genes were highly expressed in the LR group, indicating a tendency towards an impaired immune response and leptin resistance. Moreover, the moderate energy-restricted diet was able to down-regulate the inflammatory 'mitogen-activated protein kinase signalling pathway' in the HR group, as well as some inflammatory genes (AREG and TNFAIP3). The present study confirms that changes in the gene expression profile of PBMC in obese boys may help to understand the weight-loss response. However, further research is required to confirm these findings.
Autores: Abete Goñi, Itziar; Gómez Úriz, Ana; Mansego Talavera, María Luisa; et al.
ISSN 1567-2026  Vol. 12  Nº 4  2015  págs. 321 - 333
Ischemic stroke patients often show high concentrations of circulating inflammatory markers that are associated with increased risk of recurrence. Epigenetic mechanisms could be involved in obesity, inflammation and stroke. The objective of this research was to investigate, in obese patients suffering a previous stroke, the effects of a nutritional program on anthropometric and biochemical variables, and on the methylation patterns of two stroke-related genes (KCNQ1: potassium channel, voltage gated KQT-like subfamily Q, member 1; and WT1: Wilms tumor 1). Twenty-two ischemic stroke patients were compared with a control group composed of eighteen obese subjects with similar age and body mass index ranges. Both groups followed a 20-week nutritional program based on an energy-restricted balanced diet with high adherence to the Mediterranean dietary pattern. The intervention significantly improved anthropometric and metabolic variables, such as the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and C-reactive protein concentration, in ischemic stroke patients, and was accompanied by changes in the methylation patterns of both stroke-related genes, which correlated with anthropometric and biochemical variables.
Autores: Cordero Sánchez, Paul; González Muniesa, Pedro; Milagro Yoldi, Fermín Ignacio; et al.
ISSN 0931-2439  Vol. 99  Nº 5  2015  págs. 834 - 840
Maternal nutrition during pregnancy and lactation influences offspring development and health. Novel studies have described the effects on next generation obesity-related features depending on maternal macro- and micro-nutrient perinatal feeding. We hypothesized that the maternal obesogenic diet during pregnancy and lactation programs an obese phenotype, while maternal micronutrient supplementation at these stages could partially prevent these features. Thus, the aim was to assess the influence of a perinatal maternal feeding with an obesogenic diet enriched in fat and sucrose and a micronutrient supplementation during pregnancy and lactation on offspring growth and obese phenotypical features during life course. Female Wistar rats were assigned to four dietary groups during pregnancy and lactation: control, control supplemented with micronutrients (choline, betaine, folic acid and vitamin B12 ), high-fat sucrose (HFS) and HFS supplemented. At weaning, the offspring were transferred to a chow diet, and weight and fat mass were measured at weeks 3, 12 and 20. At birth, both male and female offspring from mothers fed the obesogenic diet showed lower body weight (-5 and -6%, respectively), while only female offspring weight decreased by maternal micronutrient supplementation (-5%). During lactation, maternal HFS diet was associated with increased body weight, while micronutrient supplementation protected against body weight gain. Whole body fat mass content increased at weeks 3, 12 and 20 (from 16 to 65%) due to maternal HFS diet. Maternal micronutrient supplementation decreased offspring fat mass content at week 3 (-8%). Male offspring showed higher adiposity than females at weeks 12 and 20. In conclusion, maternal HFS feeding during pregnancy and lactation was associated with a low offspring weight at birth and obese phenotypical features during adult life in a sex- and time-dependent manner. Furthermore, maternal methyl donor supplementation protected against body weight gain in male offspring during lactation and in female offspring also during juvenile period.
Autores: González Muniesa, Pedro; Quintero del Rivero, Pablo; De Andrés, J.; et al.
ISSN 1520-9512  Vol. 19  Nº 1  2015  págs. 7 - 8
Autores: González Muniesa, Pedro; García-Gerique, L.; Quintero del Rivero, Pablo; et al.
ISSN 1942-0900  Vol. 2015  2015  págs. 8957827
Several studies have shown a pathological oxygenation (hypoxia/hyperoxia) on the adipose tissue in obese subjects. Additionally, the excess of body weight is often accompanied by a state of chronic low-degree inflammation. The inflammation phenomenon is a complex biological response mounted by tissues to combat injurious stimuli in order to maintain cell homeostasis. Furthermore, it is believed that the abnormal oxygen partial pressure occurring in adipose tissue is involved in triggering inflammatory processes. In this context, oxygen is used in modern medicine as a treatment for several diseases with inflammatory components. Thus, hyperbaric oxygenation has demonstrated beneficial effects, apart from improving local tissue oxygenation, on promoting angiogenesis, wound healing, providing neuroprotection, facilitating glucose uptake, appetite, and others. Nevertheless, an excessive hyperoxia exposure can lead to deleterious effects such as oxidative stress, pulmonary edema, and maybe inflammation. Interestingly, some of these favorable outcomes occur under high and low oxygen concentrations. Hereby, we review a potential therapeutic approach to the management of obesity as well as the oxygen-related inflammation accompanying expanded adipose tissue, based on elevated oxygen concentrations. To conclude, we highlight at the end of this review some areas that need further clarification.
Autores: González Muniesa, Pedro; Garcia-Gerique, L.; Quintero del Rivero, Pablo; et al.
ISSN 1942-0900  2015  págs. 8957827
Several studies have shown a pathological oxygenation (hypoxia/hyperoxia) on the adipose tissue in obese subjects. Additionally, the excess of body weight is often accompanied by a state of chronic low-degree inflammation. The inflammation phenomenon is a complex biological response mounted by tissues to combat injurious stimuli in order to maintain cell homeostasis. Furthermore, it is believed that the abnormal oxygen partial pressure occurring in adipose tissue is involved in triggering inflammatory processes. In this context, oxygen is used in modern medicine as a treatment for several diseases with inflammatory components. Thus, hyperbaric oxygenation has demonstrated beneficial effects, apart from improving local tissue oxygenation, on promoting angiogenesis, wound healing, providing neuroprotection, facilitating glucose uptake, appetite, and others. Nevertheless, an excessive hyperoxia exposure can lead to deleterious effects such as oxidative stress, pulmonary edema, and maybe inflammation. Interestingly, some of these favorable outcomes occur under high and low oxygen concentrations. Hereby, we review a potential therapeutic approach to the management of obesity as well as the oxygen-related inflammation accompanying expanded adipose tissue, based on elevated oxygen concentrations. To conclude, we highlight at the end of this review some areas that need further clarification.
Autores: González Muniesa, Pedro; Marrades Pastor, María Pilar; Martínez Hernández, Alfredo; et al.
ISSN 1422-0067  Vol. 14  Nº 9  2013  págs. 17238 - 17255
The current nutritional habits and lifestyles of modern societies favor energy overloads and a diminished physical activity, which may produce serious clinical disturbances and excessive weight gain. In order to investigate the mechanisms by which the environmental factors interact with molecular mechanisms in obesity, a pathway analysis was performed to identify genes differentially expressed in subcutaneous abdominal adipose tissue (SCAAT) from obese compared to lean male (21-35 year-old) subjects living in similar obesogenic conditions: habitual high fat dietary intake and moderate physical activity. Genes involved in inflammation (ALCAM, CTSB, C1S, YKL-40, MIF, SAA2), extracellular matrix remodeling (MMP9, PALLD), angiogenesis (EGFL6, leptin) and oxidative stress (AKR1C3, UCHL1, HSPB7 and NQO1) were upregulated; whereas apoptosis, signal transcription (CITED 2 and NR3C1), cell control and cell cycle-related genes were downregulated. Interestingly, the expression of some of these genes (C1S, SAA2, ALCAM, CTSB, YKL-40 and tenomodulin) was found to be associated with some relevant metabolic syndrome features. The obese group showed a general upregulation in the expression of inflammatory, oxidative stress, extracellular remodeling and angiogenic genes compared to lean subjects, suggesting that a given genetic background in an obesogenic environment could underlie the resistance to gaining weight and obesity-associated manifestations.
Autores: González Muniesa, Pedro; Cordero Sánchez, Paul; Campión Zabalza, Francisco Javier; et al.
ISSN 1662-4025  Vol. 6  Nº Suppl.1  2013  págs. 51
Autores: González Muniesa, Pedro; do-Amaral, C. L.; Milagro Yoldi, Fermín Ignacio; et al.
ISSN 1662-4025  Vol. 6  Nº Suppl. 1  2013  págs. 51
Autores: González Muniesa, Pedro; López Yoldi, Miguel; Bustos de Abajo, Matilde; et al.
ISSN 1662-4025  Vol. 6  Nº Suppl. 1  2013  págs. 71
Autores: González Muniesa, Pedro; Fernández Galilea, Marta; Prieto Hontoria, Pedro Luis; et al.
ISSN 1662-4025  Vol. 6  Nº Supl. 1  2013  págs. 52
Autores: Pujol Giménez, Jonai; Barreneche Huici, Jayone; González Muniesa, Pedro; et al.
ISSN 1138-7548  Vol. 69  Nº 2  2013  págs. 325 - 333
Autores: Quintero del Rivero, Pablo; González Muniesa, Pedro; García Díaz, Diego Fernando; et al.
ISSN 1138-7548  Vol. 68  Nº 4  2012  págs. 663-669
Adipose tissue often becomes poorly oxygenated in obese subjects. This feature may provide cellular mechanisms involving chronic inflammation processes such as the release of pro-inflammatory cytokines and macrophage infiltration. In this context, the purpose of the present study was to determine whether a hyperoxia exposure on mature adipocytes may influence the expression of some adipokines and involve favorable changes in specific metabolic variables. Thus, 3T3-L1 adipocytes (14 days differentiated) were treated with 95 % oxygen for 24 h. Cell viability, intra and extracellular reactive oxygen species (ROS) content, glucose uptake, as well as lactate and glycerol concentrations were measured in the culture media. Also, mRNA levels of hypoxia-inducible factor (HIF)-1 alpha, leptin, interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, peroxisome proliferator-activated receptor (PPAR)-gamma, adiponectin, and angiopoietin-related protein (ANGPTL)4 were analyzed. Hyperoxia treatment increased intra and extracellular ROS content, reduced glucose uptake and lactate release and increased glycerol release. Additionally, a higher oxygen tension led to an upregulation of the expression of IL-6, MCP-1, and PPAR-gamma, while ANGPTL4 was downregulated in the hyperoxia group with respect to control. The present data shows that hyperoxia treatment seems to produce an inflammatory response due to the release of ROS and the upregulation of pro-inflammatory adipokines, such as IL-6 and MCP-1. On the other hand, hyperoxia may have an indirect effect on insulin sensitivity due to the upregulation of PPAR-gamma signaling as well as a possible modulation of both glucose and lipid metabolic markers. To our knowledge, this is the first study analyzing the effect of hyperoxia in 3T3-L1 adipocytes.
Autores: Valdecantos Jiménez de Andrade, Pilar; Pérez Matute, Patricia; González Muniesa, Pedro; et al.
ISSN 0955-2863  Vol. 23  Nº 12  2012  págs. 1676 - 1684
Autores: Quintero del Rivero, Pablo; González Muniesa, Pedro; Martínez Hernández, Alfredo
ISSN 0393-974X  Vol. 26  Nº 3  2012  págs. 379 - 388
Obese subjects often present a low-grade chronic inflammation in the white adipose tissue, which seems to play an important role in the initiation and development of obesity-related diseases. It has been reported that this inflammatory process may be due to a hypoxic state occuring within this tissue. Oxygen is used in current medicine as a treatment for several conditions. The aim of this study is to analyze the effects of 95% O-2 on specific metabolic variables and on the expression of some genes on murine adipocytes. 3T3-L1 adipocytes were exposed during 48 h to different treatments: 95% O-2 hyperoxia (HPx group), CoCl2 (CoCl2 group), hyperoxia with CoCl2 (HPx+CoCl2 group) and 1% O-2 hypoxia (Hx group). Cell viability, intracellular ROS content, glucose utilization, lactate and glycerol concentrations were measured. Also, mRNA expression of HIF-1 alpha, GLUT-1, ANGPTL4, PPAR-gamma, adiponectin, IL-6 and MCP-1 genes was analyzed. Importantly, 95% O-2 decreased cell viability and increased intracellular ROS production. Also, glycerol and lactate release were significantly increased and decreased, respectively, in HPx treated cells. This treatment also provoked a down-regulation of GLUT-1 and ANGPTL-4, while IL-6 and MCP-1 were up-regulated. Exposure to a hyperoxia of 95% 02 provoked an inflammatory response in adipocytes. The two hypoxia-inducing conditions (CoCl2 and 1% O-2) produced different outcomes in metabolic measurements as well as in the expression of some genes (GLUT-1, ANPGTL4, PPAR-gamma and adiponectin), while it remained similar in others (HIF-1 alpha, IL-6 and MCP-1). Indeed, hyperoxia increased significantly the ROS levels and the lipolytic activity, while it reduced lactate production. In addition to the effects on inflammation, the changes in GLUT-1, ANGPTL4 and PPAR-gamma genes lead to suppose that hyperoxia may be beneficial for the hypertrophied adipose tissues of obese subjects and for improving insulin sensitivity.
Autores: Valdecantos Jiménez de Andrade, Pilar; Pérez Matute, Patricia; González Muniesa, Pedro; et al.
Revista: OBESITY
ISSN 1930-7381  Vol. 20  Nº 10  2012  págs. 1974 - 1983
Nonalcoholic steatosis is an important hepatic complication of obesity linked to mitochondrial dysfunction and oxidative stress. Lipoic acid (LA) has been reported to have beneficial effects on mitochondrial function and to attenuate oxidative stress. The sirtuin (SIRT) family has been demonstrated to play an important role in the regulation of mitochondrial function and in the activation of antioxidant defenses. In this study, we analyzed the potential protective effect of LA supplementation, via the modulation of mitochondrial defenses through the SIRT pathway, against oxidative stress associated with high-fat feeding. Wistar rats were fed a standard diet (control group (C), n = 10), a high-fat diet (obese group (OB), n = 10) and a high-fat diet supplemented with LA (OLIP, n = 10). A group pair-fed to the latter group (pair-fed OLIP group (PFO), n = 6) was also included. LA prevented hepatic triglyceride (TG) accumulation (-68.2%) and liver oxidative damage (P < 0.01) through the inhibition of hydroperoxide (H2O2) production (P < 0.001) and the stimulation of mitochondrial antioxidant defenses. LA treatment upregulated manganese superoxide dismutase (SOD2) (60.6%) and glutathione peroxidase (GPx) (100.2%) activities, and increased the reduced glutathione (GSH): oxidized glutathione (GSSG) ratio and UCP2 mRNA levels (P < 0.001-P < 0.01). Moreover, this molecule reduced oxidative damage in mitochondrial DNA (mtDNA) and increased mitochondrial copy number (P < 0.001-P < 0.01). LA treatment decreased the acetylation levels of Forkhead transcription factor 3a (Foxo3a) and PGC1 beta (P < 0.001-P < 0.01) through the stimulation of SIRT3 and SIRT1 (P < 0.001). In summary, our results demonstrate that the beneficial effects of LA supplementation on hepatic steatosis could be mediated by its ability to restore the oxidative balance by increasing antioxidant defenses through the deacetylation of Foxo3a and PGC1 beta by SIRT1 and SIRT3.
Autores: Van der Made, SM; Baumgartner, S; González Muniesa, Pedro; et al.
Revista: Current Nutrition & Food Science
ISSN 1573-4013  Vol. 8  Nº 1  2012  págs. 25 - 44
The metabolic syndrome is one of the most evident health concerns worldwide. It is characterized by several metabolic abnormalities, which include obesity, dyslipidemia, insulin resistance, increased oxidative stress, an increased pro-inflammatory state and hypertension. Nowadays, functional foods are used in the prevention and amelioration of several chronic diseases, such as the metabolic syndrome. The relation of the consumption of certain functional foods and the improvement in health status is regulated through health claims. This review focuses on the different features of the metabolic syndrome and the influence of functional foods on these aspects, involving weight management, improvement of insulin sensitivity, serum lipid profile, anti-oxidant status, inflammatory status and hypertension. The role of plant sterols, dietary fiber, soy protein, omega-3 fatty acids, coffee, vitamin E and C, isoflavones, lycopene, sodium-low foods, a high protein diet, mono-unsaturated fatty acids, minerals and thermogenic compounds is examined concerning their functional properties
Autores: Quintero del Rivero, Pablo; González Muniesa, Pedro; Martínez Hernández, Alfredo
ISSN 1662-4025  Vol. 5  Nº Suppl. 1  2012  págs. 160
Autores: Urdampilleta, A; González Muniesa, Pedro; Portillo, MP; et al.
Revista: Journal of Physiology and Biochemistry
ISSN 0034-9402  Vol. 68  Nº 2  2012  págs. 289 - 304
Obesity is an important public health problem worldwide and is a major risk factor for a number of chronic diseases such as type II diabetes, adverse cardiovascular events and metabolic syndrome-related features. Different treatments have been applied to tackle body fat accumulation and its associated clinical manifestations. Often, relevant weight loss is achieved during the first 6 months under different dietary treatments. From this point, a plateau is reached, and a gradual recovery of the lost weight may occur. Therefore, new research approaches are being investigated to assure weight maintenance. Pioneering investigations have reported that oxygen variations in organic systems may produce changes in body composition. Possible applications of intermittent hypoxia to promote health and in various pathophysiological states have been reported. The hypoxic stimulus in addition to diet and exercise can be an interesting approach to lose weight, by inducing higher basal noradrenalin levels and other metabolic changes whose mechanisms are still unclear. Indeed, hypoxic situations increase the diameter of arterioles, produce peripheral vasodilatation and decrease arterial blood pressure. Furthermore, hypoxic training increases the activity of glycolytic enzymes, enhancing the number of mitochondria and glucose transporter GLUT-4 levels as well as improving insulin sensitivity. Moreover, hypoxia increases blood serotonin and decreases leptin levels while appetite is suppressed. These observations allow consideration of the hypothesis that intermittent hypoxia induces fat loss and may ameliorate cardiovascular health, which might be of interest for the treatment of obesity. This new strategy may be useful and practical for clinical applications in obese patients
Autores: González Muniesa, Pedro; de Oliveira, C.; Pérez de Heredia, F.; et al.
ISSN 1661-6499  Vol. 4  Nº 3  2011  págs. 146 - 153
Background/Aims: Hypoxia occurs in white adipose tissue in obesity, modulating the expression and release of specific inflammation-related adipokines. ANGPTL4 (angiopoietin-like protein 4/fasting-induced adipose factor), which is implicated in angiogenesis, lipid metabolism and glucose homeostasis, is a major hypoxia-sensitive gene; recent studies indicate that ANGPTL4 expression is also regulated by fatty acids. We have examined the effects of hypoxia and fatty acids, alone and together, on the expression and release of ANGPTL4 by human adipocytes. Methods: Human adipocytes were differentiated and incubated with fatty acids (250 mu M) in normoxia (21% O(2)) or hypoxia (1% O(2)). ANGPTL4 mRNA was measured by real-time PCR and the protein in the medium determined by ELISA. Results: In normoxia, ANGPTL4 gene expression was upregulated by palmitic, oleic, arachidonic and eicosapentaenoic acids, and ANGPTL4 release was increased. In contrast, there was no effect of lauric or myristic acids. Hypoxia alone increased the expression and secretion of ANGPTL4, and lauric, myristic, arachidonic and eicosapentaenoic acids each further increased expression and release in hypoxic adipocytes. Conclusion: The expression and secretion of ANGPTL4 by human adipocytes is upregulated by both hypoxia and fatty acids. The stimulatory effect of fatty acids on ANGPTL4 production is augmented under hypoxic conditions.
Autores: Marrades Pastor, María Pilar; González Muniesa, Pedro; Arteta, David; et al.
ISSN 1138-7548  Vol. 67  Nº 1  2011  págs. 15 - 26
There are major variations in the susceptibility to weight gain among individuals under similar external influences (decreased physical activity and excessive calorie intake), depending on the genetic background. In the present study, we performed a microarray analysis and real-time PCR validations in order to find out differential gene expression in subcutaneous abdominal adipose tissue from two groups of subjects that despite living in similar environmental conditions such as a habitual high-fat dietary intake (energy as fat >40%) and similar moderate physical activity, some of them were successfully "resistant" (lean) to weight gain, while others were "susceptible" to fat deposition (obese). The classification of up- and downregulated genes into different categories, together with the analysis of the altered biochemical pathways, revealed a coordinated downregulation of catabolic pathways operating in the mitochondria: fatty acid ß oxidation (P¿=¿0.008), tricarboxylic acid cycle (P¿=¿0.001), and electron transport chain (P¿=¿0.012). At the same time, glucose metabolism (P¿=¿0.010) and fatty acid biosynthesis (P¿=¿0.011) pathways were also downregulated in obese compared to lean subjects. In conclusion, our data showed an orchestrated downregulation of nuclear-encoded mitochondrial gene expression. These genes are involved in cellular respiration and oxidative metabolic pathways and could play a role in the susceptibility to weight gain in some individuals.
Autores: Paternain Markinez, Laura; García Díaz, Diego Fernando; Milagro Yoldi, Fermín Ignacio; et al.
Revista: Physiology & Behavior
ISSN 0031-9384  Vol. 103  Nº 2  2011  págs. 173 - 180
Autores: Urdampilleta, A.; Martínez Sanz, J. M.; González Muniesa, Pedro
Revista: Nutricion Clinica-dietetica hospitalaria
ISSN 0211-6057  Vol. 30  Nº 3  2010  págs. 27 - 41
Autores: Marrades Pastor, María Pilar; González Muniesa, Pedro; Martínez Hernández, Alfredo; et al.
ISSN 1662-4025  Vol. 3  Nº 5  2010  págs. 312 - 318
Objective: The aim of the present study was to investigate the relationship between the differential expression of genes related to lipid metabolism in subcutaneous adipose tissue and metabolic syndrome features in lean and obese subjects with habitual high fat intake. Methods: Microarray and RT-PCR analysis were used to analyze and validate differential gene expression in subcutaneous abdominal adipose tissue samples from lean and obese phenotype subjects. Results: Several genes and transcripts involved in lipolysis were down-regulated, such as AKAP1, PRKAR2B, Gi and CIDEA, whereas NPY1R and CES1 were up-regulated, when comparing obese to lean subjects. Similarly, transcripts associated with cholesterol and lipoprotein metabolism showed a differential expression, with APOE and ABCA being decreased and VLDLR being increased in obese versus lean subjects. In addition, positive correlations were found between different markers of the metabolic syndrome and CES1 and NPY1R mRNA expressions, while APOE showed an inverse association with some of them. Conclusion: Different expression patterns in transcripts encoding for proteins involved in lipolysis and lipoprotein metabolism were found between lean and obese subjects. Moreover, the dysregulation of genes such as CES1 and APOE seems to be associated with some physiopathological markers of insulin resistance and cardiovascular risk factors in obesity.
Autores: González Muniesa, Pedro; Bing, C.; Trayhurn, P.
ISSN 0018-5043  Vol. 42  Nº 10  2010  págs. 710 - 717
Inflammation in adipose tissue is a characteristic of obesity and the metabolic syndrome. It is suggested that the endocannabinoid system is involved in the regulation of inflammatory and angiogenic processes within the tissue. Human subcutaneous preadipocytes (Zen Bio) were used as the source of human preadipocytes or adipocytes. Gene expression was examined by RT-PCR and real-time PCR. The secretion of inflammation-related proteins was determined by an ELISA array. In experiments on adipocytes treated at day 14 post-differentiation, JTE-907, a synthetic cannabinoid, upregulated the expression of key inflammatory markers - IL-6, MCP-1 and IL-1 beta - and angiogenic factors - VEGF and ANGPTL4 - at 10 microM after 20 h of treatment, having also increased the expression of TRPV1 at 10 microM. JTE-907 showed no effect after 4 h. The ELISA array showed a 2.6-fold increase in IL-6 protein release. The effect of JTE-907 was inhibited by AM251 (CB1 antagonist), and partially by arachidonyl serotonin (TRPV1 and FAAH antagonist). The CB2 antagonist, AM630, partially upregulated the effect of JTE-907. Preadipocytes fed 14 days after 100% confluence exhibited downregulation of CB1, MCP-1, and IL-1 beta, 20 h after having been exposed to JTE-907. CB1 and TRPV1 receptors participate in the regulation of several inflammatory and angiogenic factors in human adipocytes, indicating their potential value as targets for the treatment of disorders related to obesity.
Autores: Martínez Fernández, Leyre; Fernández Galilea, Marta; Félix Soriano, Elisa; et al.
Libro:  Obesity: Oxidative Stress and Dietary Antioxidants
2018  págs. 63 - 92
Autores: Prieto Hontoria, Pedro Luis; Valdecantos Jiménez de Andrade, Pilar; González Muniesa, Pedro
Libro:  Fundamentos de Nutrición y dietética. Bases metodológicas y aplicaciones
2010  págs. 359 - 362


C.4. Patentes

C.5. Cargos institucionales Responsable del área de relaciones internacionales de Nutrición Humana y Dietética. Coordinador del ¿International Nutrition Certificate¿ y del ¿International Pharmaceutical Certificate¿, títulos propios de la Facultad de Farmacia y Nutrición, de la Universidad de Navarra.

C.6. Tesis doctorales dirigidas
Pablo Quintero del Rivero; Título: Efectos metabólicos y transcriptómicos de diferentes concentraciones de oxígeno: modelos in vivo e in vitro; Defensa: 2012; Beca Asociación de Amigos (Universidad de Navarra); Universidad de Navarra. Co-director.
Anita Schella; Título: Extra virgin olive oil intake and the lower likelyhood of being obese, hypertensive and diabetic; Defensa: 2015; University of Calabria (Italia) / Universidad de Navarra. Co-director.
Amaya López Pascual; Título: Efectos de la terapia de oxígeno sobre marcadores genéticos y bioquímicos del metabolismo y la inflamación in vitro e in vivo; Defensa: 2018; Beca FPU; Universidad de Navarra. Director.
Leyre Martínez Fernández; Título: Mediadores lipídicos derivados de los ácidos grasos omega-3: acciones sobre el metabolismo glucídico, la insulino-resistencia y la producción de adipoquinas en obesidad; Defensa: 2018; Beca FPI; Universidad de Navarra. Co-director.

C.7. Redes de investigación a las que pertenece o ha pertenecido
-Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición (CIBERobn), actualmente -IdiSNA (Instituto de Investigación Sanitaria de Navarra), actualmente. -CENIT Pronaos (finalizado en 2012)

C.8. Actividades de Edición, Revisión o Evaluación
-Editor ejecutivo de la revista Journal of Phisiology and Biochemistry y Editor invitado de un número especial de la revista International Journal of Molecular Sciences, de un Supplement de la revista Journal of Nutrigenetics and Nutrigenomics y de la revista Integrative Medicine Insights, y Editor invitado coordinador de un número especial de la revista Oxidative Medicine and Cellular Longevity. -Revisor para 14 revistas científicas de los campos de la nutrición y dietética, farmacología, endocrinología y metabolismo, biología, bioquímica y biología molecular. -He recibido 4 becas para asistir a cursos o para la realización de la tesis doctoral, como la del Instituto Danone, además de la beca Socrates, como alumno de intercambio. -Evaluador para el programa de proyectos de investigación ZonMW Vidi de Holanda (para investigadores experimentados), 2013-2014 y 2014-2015. -Evaluador de propuestas de proyectos de investigación para el "National Science Centre" de Polonia. 2015.