Nuestros investigadores

María Jesús Moreno Aliaga

Departamento
Ciencias de la Alimentación y Fisiología
Facultad de Farmacia y Nutrición. Universidad de Navarra
Líneas de investigación
Genómica nutricional del tejido adiposo en obesidad: metabolismo lipídico y glucídico, secreción de adipoquinas, pardeamiento, Papel de Cardiotrofina-1 y otras citoquinas de la familia de IL-6 en tejido adiposo e intestino en obesidad y complicaciones metabólicas asociadas, Ácido lipoico y obesidad: análisis de los mecanismos moleculares implicados, Ácidos grasos omega-3 y mediadores lipídicos bioactivos derivados en obesidad, inflamación e insulino-resistencia, Sexenios CNEAI: 3 (1995-2003; 2004-2009; 2010-2015)

Publicaciones científicas más recientes (desde 2010)

Autores: Yang, J. C. Z.; Fernández, Marta; et al.
Revista: NUTRIENTS
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: Gessani, S., (Autor de correspondencia); Van Duijnhoven, F. J.; Moreno-Aliaga MJ;
Revista: FRONTIERS IN IMMUNOLOGY
ISSN 1664-3224  Vol. 10  2019 
Autores: Vela, S.; Sáinz, Neira; Moreno-Aliaga MJ; et al.
Revista: MOLECULAR NEUROBIOLOGY
ISSN 0893-7648  Vol. 56  Nº 3  2019  págs. 1618 - 1627
A potential role of marine n-3 polyunsaturated fatty acids (-3 PUFAs) has been suggested in memory, learning, and cognitive processes. Therefore, -3 PUFAs might be a promising treatment option, albeit controversial, for Alzheimer's disease (AD). Among the different mechanisms that have been proposed as responsible for the beneficial effects of -3 PUFAs, inhibition of JNK stands as a particularly interesting candidate. In the present work, it has been studied whether the administration of two different PUFAs (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) and a DHA-derived specialized pro-resolving lipid mediator (MaR1) is able to reverse cognitive deficits in the senescence-accelerated mouse prone 8 (SAMP8) mouse model of sporadic AD. The novel object recognition test (NORT) test showed that recognition memory was significantly impaired in SAMP8 mice, as shown by a significantly decreased discrimination index that was reversed by MaR1 and DHA. In the retention phase of the Morris water maze (MWM) task, SAMP8 mice showed memory deficit that only DHA treatment was able to reverse. pJNK levels were significantly increased in the hippocampus of SAMP8 mice compared to SAMR1 mice, and only DHA treatment was able to significantly reverse these increased pJNK levels. Similar results were found when measuring c-Jun, the main JNK substrate. Consequently to the increases in tau phosphorylation after increased pJNK, it was checked that tau phosphorylation (PHF-1) was increased in SAMP mice, and this effect was reversed after DHA treatment. Altogether, DHA could represent a new approach for the treatment of AD through JNK inhibition.
Autores: Valdecantos, M. P.; Pérez-Matute, P., (Autor de correspondencia); Prieto-Hontoria, P.; et al.
Revista: INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION
ISSN 0963-7486  Vol. 70  Nº 7  2019  págs. 834 - 844
The aim of this study was to examine the effects of ¿-lipoic acid (¿-LA) on liver mitochondrial bioenergetics and oxidative status for 8¿weeks in normal-healthy animals. A pair-fed group was included to differentiate between ¿-LA direct effects and those changes due to reduced food intake. ¿-LA decreased body weight gain, liver weight and insulin levels with no differences compared to its pair-fed group. ¿-LA significantly reduced energy efficiency, the activity of the electron transport chain complexes and induced a lower efficiency of oxidative phosphorylation with reduced ATP production. ¿-LA supplementation directly decreased plasma triglycerides (TGs), free fatty acids and ketone bodies levels. A significant reduction in hepatic TG content was also observed. A significant up-regulation of Cpt1a, Acadl and Sirt3, all ß-oxidation genes, along with a significant deacetylation of the forkhead transcription factor 3a (FOXO3A) was found in ¿-LA-treated animals. Thus, ¿-LA along with a standard chow diet has direct actions on lipid metabolism and liver by modulating mitochondrial function in normal-weight rats. These results should be taken into account when ¿-LA is administered or recommended to a healthy population.
Autores: Arbones-Mainar, J. M. ; Moreno-Aliaga MJ; et al.
Revista: ACTA PHYSIOLOGICA
ISSN 1748-1708  Vol. 226  Nº 4  2019 
AimThe facilitative glucose transporter GLUT12 was isolated from the breast cancer cell line MCF-7 by its homology with GLUT4. GLUT12 is expressed in insulin-sensitive tissues such as adipose tissue. The aim of this work was to investigate GLUT12 expression and hormonal regulation in 3T3-L1 adipocytes and in adipose tissue of lean and diet-induced obese mice. MethodsUptake studies were performed using radio-labelled sugars; alpha-methyl-d-glucose (alpha MG) was used as specific substrate of GLUT12. Expression and localization of GLUT12 in adipocytes were investigated by western blot and immunohistochemical methods. ResultsGLUT12 is expressed in the peri-nuclear region of mouse adipocytes. Insulin, by AKT activation, and TNF-alpha, by AMPK activation, increase alpha MG uptake by inducing GLUT12 translocation to the membrane. In contrast, leptin and adiponectin decrease GLUT12 activity through its internalization. Under hypoxia conditions GLUT12 expression is upregulated. The response of GLUT12 to TNF-alpha, leptin, adiponectin and hypoxia is the opposite to that of GLUT4. In diet-induced obese mice and obese subjects, GLUT12 protein is decreased. Intraperitoneal injection of insulin increases AKT phosphorylation and GLUT12 expression, but this effect is lost in obese animals. ConclusionWe hypothesize that GLUT12 would contribute to modulate sugar absorption in physiological and pathophysiological situations such as obesity.
Autores: González-Muniesa, P; Sáinz, Neira; et al.
Revista: MOLECULAR NUTRITION & FOOD RESEARCH (ONLINE)
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: Castilla, Rosa María; Sáinz, Neira; et al.
Revista: JOURNAL OF CELLULAR PHYSIOLOGY
ISSN 0021-9541  Vol. 234  Nº 4  2019  págs. 4352 - 4361
We have previously demonstrated in Caco-2 cells that tumor necrosis factor-alpha (TNF-alpha) inhibits sugar uptake, acting from the apical membrane, by decreasing the expression of the Na+-glucose cotransporter SGLT1 in the brush border membrane. The goal was to investigate the hypothesis that TNF-alpha from abdominal adipose tissue (adipocytes and macrophages) would decrease sugar and amino acid transport acting from the basolateral membrane of the enterocytes. TNF-alpha placed in the basal compartment of Caco-2 cells decreased alpha-methyl- d-glucose (alphaMG) and glutamine uptake. The apical medium derived from these Caco-2 cells apically placed in another set of cells, also reduced sugar and glutamine transport. Reverse-transcription polymerase chain reaction analysis demonstrated upregulation of TNF-alpha, IL-1beta, and MCP1 expression in Caco-2 cells exposed to basal TNF-alpha. Similarly, MG uptake was inhibited after Caco-2 cells were incubated, in the basal compartment, with medium from visceral human mesenchymal stem cells-derived adipocytes of overweight individuals. The apical medium collected from those Caco-2 cells, and placed in the upper side of other set of cells, also decreased sugar uptake. Basal presence of medium derived from lipopolysaccharide-activated macrophages and nonactivated macrophages decreased MG uptake as well. Diet-induced obese mice showed an increase in the visceral adipose tissue surrounding the intestine.
Autores: Martinez-Hernandez, L.; González-Muniesa, P; Sáinz, Neira; et al.
Revista: ANNALS OF NUTRITION AND METABOLISM
ISSN 0250-6807  Vol. 75  2019  págs. 23
Autores: Ramos-Lopez, O.; Riezu-Boj, José Ignacio; Milagro FI; et al.
Revista: ADIPOCYTE
ISSN 2162-3945  Vol. 7  Nº 2  2018  págs. 137 - 142
Unresolved ER stress is involved in the onset and progression of several obesity-related metabolic disorders, including dyslipidemia and insulin resistance. Different epigenetic modifications may regulate ER stress response and consequently disease risks. These epigenetic phenomena encompass DNA and histone methylation patterns in ER stress genes and downstream signaling molecules, as well as microRNA expression. Our results suggest potential associations of methylation signatures at ER regulatory genes in white blood cells with an abdominal/central obesity marker (waist circumference), dyslipidemia, and insulin resistance. Interestingly, most of these genes were implicated in ER stress, as revealed by pathway enrichment analysis. Together, these findings add knowledge into the current understanding of relationships between obesity and accompanying complications with epigenetics and ER stress. Here, we comment about the implication of ER stress in central/abdominal adiposity, dyslipidemia, and insulin resistance, with an emphasis on the role that epigenetics may play on these pathological processes.
Autores: Lorente, Silvia; Martinez-Fernandez, L.; et al.
Revista: INTERNATIONAL JOURNAL OF OBESITY
ISSN 0307-0565  Vol. 42  Nº 3  2018  págs. 572 - 579
BACKGROUND/OBJECTIVES: The aim of this study was to characterize the effects of Maresin 1 (MaR1) in obesity-related liver steatosis and the mechanisms involved. METHODS: MaR1 effects on fatty liver disease were tested in ob/ob (2-10 mu g kg(-1) i.p., 20 days) and in diet-induced obese (DIO) mice (2 mu g kg(-1), i.p., or 50 mu g kg(-1), oral gavage for 10 days), as well as in cultured hepatocytes. RESULTS: In ob/ob mice, MaR1 reduced liver triglycerides (TG) content, fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 protein expression, while increased acetyl-CoA carboxylase (ACC) phosphorylation and LC3II protein expression, in parallel with a drop in p62 levels. Similar effects on hepatic TG, ACC phosphorylation, p62 and LC3II were observed in DIO mice after MaR1 i.p. injection. Interestingly, oral gavage of MaR1 also decreased serum transaminases, reduced liver weight and TG content. MaR1-treated mice exhibited reduced hepatic lipogenic enzymes content (FAS) or activation (by phosphorylation of ACC), accompanied by upregulation of carnitine palmitoyltransferase (Cpt1a), acyl-coenzyme A oxidase (Acox1) and autophagy-related proteins 5 and 7 (Atg5-7) gene expression, along with increased number of autophagic vacuoles and reduced p62 protein levels. MaR1 also induced AMP-activated protein kinase (AMPK) phosphorylation in DIO mice and in primary hepatocytes, and AMPK inhibition completely blocked MaR1 effects on Cpt1a, Acox1, Atg5 and Atg7 expression. CONCLUSIONS: MaR1 ameliorates liver steatosis by decreasing lipogenic enzymes, while inducing fatty acid oxidation genes and autophagy, which could be related to AMPK activation. Thus, MaR1 may be a new therapeutic candidate for reducing fatty liver in obesity.
Autores: Santiago, Susana; Bes-Rastrollo, Maira; et al.
Revista: INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
ISSN 1660-4601  Vol. 15  Nº 10  2018  págs. E2104
The aim of this study was to investigate determinants of self-rated health (SRH) perception in Spanish adults. This cross-sectional study including data from 11,342 participants from the Spanish PLENUFAR VI study. SRH status was grouped in two categories ('good'/'poor') and the associations of socio-demographic characteristics, lifestyles, diet adequacy and chronic disease with SRH were assessed. After adjusting for relevant confounders, the risk ratios (RR) and (95% confidence intervals) for poor SRH were 1.05 (1.03-1.07) for each hour of increment of sitting, 1.56 (1.30-1.88) for short (>= 5 h vs. 7-8 h) sleep duration, 0.63 (0.55-0.72) for vigorous (vs. light) physical activity, 0.61 (0.50-0.74) for adequate (vs. non-adequate) diet. Activities like jogging [RR for each unit of increment in the METs-h/day = 0.87 (0.82-0.92)], gymnastics [0.87 (0.81-0.93)], biking [0.91 (0.85-0.98)], and track and field [0.94 (0.89-0.98)], were associated with better health perception. Normally weight participants with any chronic disease had lower probability to report poor SRH than overweight/obese participants with any chronic disease. Frequent consumption of bread (>2 servings/day) was associated with a lower adjusted mean of health perception scale, while higher consumption of vegetables and fruit or fish were associated with higher values, concerning good SRH. We can conclude that normal-weight participants even suffering a chronic disease had lower probability to report poor health perception than participants with overweight/obesity and a chronic disease especially for hypertension and diabetes. Activities like jogging, gymnastics, biking, and track and field, and a higher consumption of fruits, vegetables and fish, were associated with better health rated perception.
Autores: Lorente, Silvia; et al.
Revista: JOURNAL OF CELLULAR PHYSIOLOGY
ISSN 0021-9541  Vol. 233  Nº 3  2018  págs. 2238 - 2246
Obesity is associated with high levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-¿), which promotes inflammation in adipose tissue. The omega-3 PUFAs, and their derived lipid mediators, such as Maresin 1 (MaR1) have anti-inflammatory effects on adipose tissue. This study aimed to analyze if MaR1 may counteract alterations induced by TNF-¿ on lipolysis and autophagy in mature 3T3-L1 adipocytes. Our data revealed that MaR1 (1-100¿nM) inhibited the TNF-¿-induced glycerol release after 48¿hr, which may be related to MaR1 ability of preventing the decrease in lipid droplet-coating protein perilipin and G0/G1 Switch 2 protein expression. MaR1 also reversed the decrease in total hormone sensitive lipase (total HSL), and the ratio of phosphoHSL at Ser-565/total HSL, while preventing the increased ratio of phosphoHSL at Ser-660/total HSL and phosphorylation of extracellular signal-regulated kinase 1/2 induced by TNF-¿. Moreover, MaR1 counteracted the cytokine-induced decrease of p62 protein, a key autophagy indicator, and also prevented the induction of LC3II/LC3I, an important autophagosome formation marker. Current data suggest that MaR1 may ameliorate TNF-¿-induced alterations on lipolysis and autophagy in adipocytes. This may also contribute to the beneficial actions of MaR1 on adipose tissue and insulin sensitivity in obesity.
Autores: Gonzalez-Rodriguez, A., (Autor de correspondencia); Valdecantos, M. P. ; Rada, P. ; et al.
Revista: MOLECULAR METABOLISM
ISSN 2212-8778  Vol. 7  2018  págs. 132 - 146
Objectives: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries. Protein tyrosine phosphatase 1B (PTP1B), a negative modulator of insulin and cytokine signaling, is a therapeutic target for type 2 diabetes and obesity. We investigated the impact of PTP1B deficiency during NAFLD, particularly in non-alcoholic steatohepatitis (NASH). Methods: NASH features were evaluated in livers from wild-type (PTP1BWT) and PTP1B-deficient (PTP1BKO) mice fed methionine/choline-deficient diet (MCD) for 8 weeks. A recovery model was established by replacing MCD to chow diet (CHD) for 2-7 days. Non-parenchymal liver cells (NPCs) were analyzed by flow cytometry. Oval cells markers were measured in human and mouse livers with NASH, and in oval cells from PTP1BWT and PTP1BKO mice. Results: PTP1BWT mice fed MCD for 8 weeks exhibited NASH, NPCs infiltration, and elevated Fgf21, II6 and II1b mRNAs. These parameters decreased after switching to CHD. PTP1B deficiency accelerated MCD-induced NASH. Conversely, after switching to CHD, PTP1BKO mice rapidly reverted NASH compared to PTP1BWT mice in parallel to the normalization of serum triglycerides (TG) levels. Among NPCs, a drop in cytotoxic natural killer T (NKT) subpopulation was detected in PTP1BKO livers during recovery, and in these conditions M2 macrophage markers were up regulated. Oval cells markers (EpCAM and cytokeratin 19) significantly increased during NASH only in PTP1B-deficient livers. HGF-mediated signaling and proliferative capacity were enhanced in PTP1BKO oval cells. In NASH patients, oval cells markers were also elevated. Conclusions: PTP1B elicits a dual role in NASH progression and reversion. Additionally, our results support a new role for PTP1B in oval cell proliferation during NAFLD. (C) 2017 The Authors. Published by Elsevier GmbH.
Autores: Lopez-Pascual, A. ; Lorente, Silvia; Moreno-Aliaga MJ; et al.
Revista: JOURNAL OF CELLULAR PHYSIOLOGY
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: Romo, Ana; Huerta, Ana Elsa; González-Navarro, CJ; et al.
Revista: LIPIDS IN HEALTH AND DISEASE
ISSN 1476-511X  Vol. 17  2018  págs. 103
Background: Eicosapentaenoic acid (EPA) and alpha-lipoic acid (alpha-LA) have been investigated for their beneficial effects on obesity and cardiovascular risk factors. In the current research, the goal was to evaluate metabolomic changes following the dietary supplementation of these two lipids, alone or combined in healthy overweight/obese sedentary women following an energy-restricted diet. For this purpose, an untargeted metabolomics approach was conducted on urine samples using liquid chromatography coupled with time of flight mass spectrometry (HPLC-TOF-MS). Methods: This is a short-term double blind placebo-controlled study with a parallel nutritional design that lasted 10 weeks. Participants were assigned to one of the 4 experimental groups [Control, EPA (1.3 g/d), alpha-LA (0.3 g/d) and EPA+alpha-LA (1.3 g/d + 0.3 g/d)]. All intervention groups followed an energy-restricted diet of 30% less than total energy expenditure. Clinically relevant biochemical measurements were analyzed. Urine samples (24 h) were collected at baseline and after 10 weeks. Untargeted metabolomic analysis on urine samples was carried out, and principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were performed for the pattern recognition and characteristic metabolites identification. Results: Urine samples were scattered in the PCA scores plots in response to the supplementation with alpha-LA. Totally, 28 putative discriminant metabolites in positive ionization, and 6 in negative ionization were identified among groups clearly differentiated according to the a-LA administration. Remarkably is the presence of an ascorbate intermediate metabolite (one of the isomers of trihydroxy-dioxohexanoate, or dihydroxy-oxohexanedionate) in the groups supplemented with aLA. This fact might be associated with antioxidant properties of both alpha-LA and ascorbic acid. Correlations between phenotypical parameters and putative metabolites of provided additional information on whether there is a direct or inverse relationship between them. Especially interesting are the negative correlation between ascorbate intermediate metabolite and asymmetric dimethylarginine (ADMA) and the positive one between superoxide dismutase (SOD) and aLA supplementation. Conclusions: This metabolomic approach supports that the beneficial effects of alpha-LA administration on body weight reduction may be partly explained by the antioxidant properties of this organosulfur carboxylic acid mediated by isomers of trihydroxy-dioxohexanoate, or dihydroxy-oxohexanedionate.
Autores: Escoté, Xavier; et al.
Revista: FOOD & FUNCTION
ISSN 2042-6496  Vol. 9  Nº 5  2018  págs. 3028 - 3036
FGF21 has emerged as a key metabolism and energy homeostasis regulator. Dietary supplementation with eicosapentaenoic acid (EPA) and/or -lipoic acid (LIP) has shown beneficial effects on obesity. In this study, we evaluated EPA and/or LIP effects on plasma FGF21 and the fatty acid (FA) profile in overweight/obese women following hypocaloric diets. At the baseline, FGF21 levels were negatively related to the AST/ALT ratio and HMW adiponectin. The weight loss did not cause any significant changes in FGF21 levels, but after the intervention FGF21 increased in EPA-supplemented groups compared to non-EPA-supplemented groups. EPA supplementation decreased the plasma n-6-PUFA content and increased n-3-PUFAs, mainly EPA and DPA, but not DHA. In the LIP-alone supplemented group a decrease in the total SFA and n-6-PUFA content was observed after the supplementation. Furthermore, EPA affected the desaturase activity, lowering 4D and raising 5/6D. These effects were not observed in the LIP-supplemented groups. Besides, the changes in FGF21 levels were associated with the changes in EPA, n-3-PUFAs, 5/6D, and n-6/n-3 PUFA ratio. Altogether, our study suggests that n-3-PUFAs influence FGF21 levels in obesity, although the specific mechanisms implicated remain to be elucidated.
Autores: Castilla, Rosa María; Moreno-Aliaga MJ; et al.
Revista: JOURNAL OF CELLULAR PHYSIOLOGY
ISSN 0021-9541  Vol. 233  Nº 3  2018  págs. 2426 - 2433
The aim of the present work was to investigate in Caco-2 cells whether eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, could block the inhibitory effect of tumor necrosis factor-alpha (TNF-alpha) on sugar transport, and identify the intracellular signaling pathways involved. After pre-incubation of the Caco-2 cells with TNF-alpha and EPA for 1 hr, EPA prevented the inhibitory effect of the cytokine on alpha-methyl-D-glucose (alpha MG) uptake (15 min) and on SGLT1 expression at the brush border membrane, measured by Western blot. The ERK1/2 inhibitor PD98059 and the AMPK activator AICAR also prevented the inhibitory effect of TNF-alpha on both alpha MG uptake and SGLT1 expression. Interestingly, the AMPK inhibitor, Compound C, abolished the ability of EPA to prevent TNF-alpha-induced reduction of sugar uptake and transporter expression. The GPR120 antagonist, AH7614, also blocked the preventive effect of EPA on TNF-alpha-induced decrease of alpha MG uptake and AMPK phosphorylation. In summary, TNF-alpha inhibits alpha MG uptake by decreasing SGLT1 expression in the brush border membrane through the activation of ERK1/2 pathway. EPA prevents the inhibitory effect of TNF-alpha through the involvement of GPR120 and AMPK activation.
Autores: Escoté, Xavier; Huerta, Ana Elsa; Fernández, Marta; et al.
Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  págs. 206 - 206
Autores: Escoté, Xavier; Gómez-Zorita, S.; et al.
Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN 1422-0067  Vol. 18  Nº 8  2017  págs. 1770
Adipose tissue releases bioactive mediators called adipokines. This review focuses on the effects of omentin, vaspin, cardiotrophin-1, Tumor necrosis factor-like Weak Inducer of Apoptosis (TWEAK) and nephroblastoma overexpressed (NOV/CCN3) on obesity and diabetes. Omentin is produced by the stromal-vascular fraction of visceral adipose tissue. Obesity reduces omentin serum concentrations and adipose tissue secretion in adults and adolescents. This adipokine regulates insulin sensitivity, but its clinical relevance has to be confirmed. Vaspin is produced by visceral and subcutaneous adipose tissues. Vaspin levels are higher in obese subjects, as well as in subjects showing insulin resistance or type 2 diabetes. Cardiotrophin-1 is an adipokine with a similar structure as cytokines from interleukin-6 family. There is some controversy regarding the regulation of cardiotrophin-1 levels in obese -subjects, but gene expression levels of cardiotrophin-1 are down-regulated in white adipose tissue from diet-induced obese mice. It also shows anti-obesity and hypoglycemic properties. TWEAK is a potential regulator of the low-grade chronic inflammation characteristic of obesity. TWEAK levels seem not to be directly related to adiposity, and metabolic factors play a critical role in its regulation. Finally, a strong correlation has been found between plasma NOV/CCN3 concentration and fat mass. This adipokine improves insulin actions.
Autores: Huerta, Ana Elsa; Prieto, Pedro Luis; Fernández, Marta; et al.
Revista: BIOFACTORS
ISSN 0951-6433  Vol. 43  Nº 1  2017  págs. 117 - 131
In obesity, the increment of adiposity levels disrupts the whole body homeostasis, promoting an over production of oxidants and inflammatory mediators. The current study aimed to characterize the transcriptomic changes promoted by supplementation with eicosapentaenoic acid (EPA, 1.3 g/day), ¿-lipoic acid (0.3 g/day), or both (EPA¿+¿¿-lipoic acid, 1.3 g/day¿+¿0.3 g/day) in subcutaneous abdominal adipose tissue from overweight/obese healthy women, who followed a hypocaloric diet (30% of total energy expenditure) during ten weeks, by using a microarray approach. At the end of the intervention, a total of 33,297 genes were analyzed using Affymetrix GeneChip arrays. EPA promoted changes in extracellular matrix remodeling gene expression, besides a rise of genes associated with either chemotaxis or wound repair. ¿-Lipoic acid decreased expression of genes related with cell adhesion and inflammation. Furthermore, ¿-lipoic acid, especially in combination with EPA, upregulated the expression of genes associated with lipid catabolism while downregulated genes involved in lipids storage. Together, all these data suggest that some of the metabolic effects of EPA and ¿-lipoic acid could be related to their regulatory actions on adipose tissue metabolism.
Autores: Huerta, Ana Elsa; Riezu-Boj, José Ignacio; Milagro FI; et al.
Revista: JOURNAL OF FUNCTIONAL FOODS
ISSN 1756-4646  Vol. 36  2017  págs. 178 - 185
This study aims to assess methylation modifications in blood cell genes induced by eicosapentaenoic acid (EPA) and/or alpha-lipoic acid (LA) supplementation, and their potential relationship with metabolic risk biomarkers. Healthy overweight/obese women were assigned to 4 experimental groups (control or groups supplemented with 1.3 g EPA/day, 0.3 g LA/day, or both), all followed a 10-week hypocaloric diet. White blood cells DNA was hybridized in Human-450K-methylation microarray. Differentially methylated CpGs (post-pre) were identified in supplemented groups, including CpG regions from NCK2, FITM2, TRRAP, RPTOR and CREBBP genes. In peripheral blood mononuclear cells (PBMC), LA upregulated NCK2, TRRAP and RPTOR mRNA, which negatively associated with changes in body weight and fat mass. Changes in cg10320884 (TRRAP) methylation site negatively correlated with changes in TRRAP mRNA in PBMC, and positively with Framingham score. Further studies are needed to better characterize the potential involvement of epigenetics in the actions of LA and EPA.
Autores: Huerta, Ana Elsa; Riezu-Boj, José Ignacio; Milagro FI; et al.
Revista: JOURNAL OF FUNCTIONAL FOODS
ISSN 1756-4646  Vol. 36  2017  págs. 178 - 185
This study aims to assess methylation modifications in blood cell genes induced by eicosapentaenoic acid (EPA) and/or alpha-lipoic acid (LA) supplementation, and their potential relationship with metabolic risk biomarkers. Healthy overweight/obese women were assigned to 4 experimental groups (control or groups supplemented with 1.3 g EPA/day, 0.3 g LA/day, or both), all followed a 10-week hypocaloric diet. White blood cells DNA was hybridized in Human-450K-methylation microarray. Differentially methylated CpGs (post-pre) were identified in supplemented groups, including CpG regions from NCK2, FITM2, TRRAP, RPTOR and CREBBP genes. In peripheral blood mononuclear cells (PBMC), LA upregulated NCK2, TRRAP and RPTOR mRNA, which negatively associated with changes in body weight and fat mass. Changes in cg10320884 (TRRAP) methylation site negatively correlated with changes in TRRAP mRNA in PBMC, and positively with Framingham score. Further studies are needed to better characterize the potential involvement of epigenetics in the actions of LA and EPA. (C) 2017 Elsevier Ltd. All rights reserved.
Autores: Romero-Lozano, M. A.; et al.
Revista: JOURNAL OF CELLULAR PHYSIOLOGY
ISSN 0021-9541  Vol. 232  Nº 9  2017  págs. 2469 - 2477
Cardiotrophin-1 (CT-1) belongs to the IL-6 family of cytokines. Previous studies of our group revealed that CT-1 is a key regulator of glucose and lipid metabolism. The aim of the present study was to analyze the in vitro and in vivo effects of CT-1 on the production of several adipokines involved in body weight regulation, nutrient metabolism, and inflammation. For this purpose, 3T3-L1 adipocytes were incubated with recombinant protein CT-1 (rCT-1) (1-40 ng/ml) for 1 and 18 h. Moreover, the acute effects of rCT-1 administration (0.2 mg/kg, i.v.) for 30 min and 3 h on adipokines levels were also evaluated in high-fat fed obese mice. In 3T3-L1 adipocytes, rCT-1 treatment downregulated the expression and secretion of leptin, resistin, and visfatin. However, rCT-1 significantly stimulated apelin mRNA and secretion. rCT-1 (18 h) also promoted the activation by phosphorylation of AKT, ERK 1/2, and STAT3. Interestingly, pretreatment with the PI3K inhibitor LY294002 reversed the stimulatory effects of rCT-1 on apelin expression, suggesting that this pathway could be mediating the effects of rCT-1 on apelin production. In contrast, acute administration of rCT-1 (30 min and 3 h) to diet-induced obese mice downregulated leptin and resistin, without significantly modifying apelin or visfatin mRNA in adipose tissue. Furthermore, CT-1 null mice exhibited altered expression of adipokines in adipose tissue. The present study demonstrates that rCT-1 modulates the production of adipokines in vitro and in vivo, suggesting that the regulation of the secretory function of adipocytes could be involved in the metabolic actions of this cytokine. (C) 2016 Wiley Periodicals, Inc.
Autores: Huerta, Ana Elsa; Riezu-Boj, José Ignacio; Milagro FI; et al.
Revista: JOURNAL OF FUNCTIONAL FOODS
ISSN 1756-4646  Vol. 36  2017  págs. 178 - 185
This study aims to assess methylation modifications in blood cell genes induced by eicosapentaenoic acid (EPA) and/or ¿-lipoic acid (LA) supplementation, and their potential relationship with metabolic risk biomarkers. Healthy overweight/obese women were assigned to 4 experimental groups (control or groups supplemented with 1.3 g EPA/day, 0.3 g LA/day, or both), all followed a 10-week hypocaloric diet. White blood cells DNA was hybridized in Human-450K-methylation microarray. Differentially methylated CpGs (post¿pre) were identified in supplemented groups, including CpG regions from NCK2, FITM2, TRRAP, RPTOR and CREBBP genes. In peripheral blood mononuclear cells (PBMC), LA upregulated NCK2, TRRAP and RPTOR mRNA, which negatively associated with changes in body weight and fat mass. Changes in cg10320884 (TRRAP) methylation site negatively correlated with changes in TRRAP mRNA in PBMC, and positively with Framingham score. Further studies are needed to better characterize the potential involvement of epigenetics in the actions of LA and EPA.
Autores: Marti A; Rendo-Urteaga, T.; et al.
Revista: PEDIATRIC DIABETES
ISSN 1399-543X  Vol. 19  Nº 2  2017  págs. 217 - 222
BACKGROUND: Inflammation related molecules such as tumor necrosis factor-¿ (TNF-¿), interleukin 6 (IL-6), and cardiotrophin-1 (CT-1) are highly expressed in obese individuals and could partly explain some comorbidities associated to obesity. In obese children, lifestyle interventions are able to lower inflammation and reduce cardiovascular risk factors associated with obesity. The aim of the present work was to study changes in inflammation-related molecules serum and peripheral blood mononuclear cells (PBMC) transcript levels after a 10-week lifestyle intervention in obese children and asses their potential association with glucose metabolism. METHODS: Twenty-three obese children (mean age 11.5 years; 48% males) underwent a 10-week lifestyle not controlled intervention trial. Anthropometric and biochemical measurements were analyzed. Transcript analysis for CT-1, IL-6, and TNF-¿ in PBMC were performed by RT-PCR. Serum cytokine levels were also measured at baseline and after 10-weeks. RESULTS: Participants achieved a significant reduction in body adiposity (0.34 decrease in body mass index-standard deviation), total cholesterol, and glucose levels after 10-weeks. A Significant decrease in serum TNF-¿ and C reactive protein (CRP) were observed. CT-1 transcript levels were significantly reduced (P = .005) after lifestyle intervention, and these changes were significantly correlated with changes in serum CT-1 levels (r = 0.451; P = .031). In multiple regression analysis baseline CT-1 transcript levels were positively associated with final insulin (R2 = 0.506; P = .035) and HOMA-IR values (R2 = 0.473; P = .034). CONCLUSIONS: We reported that serum CRP, TNF-¿, as well as PBMC CT-1 transcript levels were reduced after lifestyle intervention in obese children. More studies are needed to clarify the role of inflammation-related molecules in glucose metabolism.
Autores: Stanhope, K. L.; Garaulet, M.; et al.
Revista: FASEB JOURNAL
ISSN 0892-6638  Vol. 31  Nº 4  2017  págs. 1639 - 1649
Cardiotrophin (CT)-1 is a regulator of glucose and lipid homeostasis. In the present study, we analyzed whether CT-1 also acts to peripherally regulate metabolic rhythms and adipose tissue core clock genes in mice. Moreover, the circadian pattern of plasma CT-1 levels was evaluated in normal-weight and overweight subjects. The circadian rhythmicity of oxygen consumption rate (Vo(2)) was disrupted in aged obese CT-1-deficient (CT-1(-/-)) mice (12 mo). Although circadian rhythms of Vo(2) were conserved in young lean CT-1(-/-) mice (2 mo), CT-1 deficiency caused a phase shift of the acrophase. Most of the clock genes studied (Clock, Bmal1, and Per2) displayed a circadian rhythm in adipose tissue of both wild-type (WT) and CT-1(-/-) mice. However, the pattern was altered in CT-1(-/-) mice toward a lower percentage of the rhythm or lower amplitude, especially for Bmal1 and Clock. Moreover, CT-1 mRNA levels in adipose tissue showed significant circadian fluctuations in young WT mice. In humans, CT-1 plasma profile exhibited a 24-h circadian rhythm in normal-weight but not in overweight subjects. The 24-h pattern of CT-1 was characterized by a pronounced increase during the night (from 02:00 to 08:00). These observations suggest a potential role for CT-1 in the regulation of metabolic circadian rhythms.-Lopez-Yoldi, M., Stanhope, K. L., Garaulet, M., Chen, X. G., Marcos-Gomez, B., Carrasco-Benso, M. P., Santa Maria, E. M., Escote, X., Lee, V., Nunez, M. V., Medici, V., Martinez-Anso, E., Sainz, N., Huerta, A. E., Laiglesia, L. M., Prieto, J., Martinez, J. A., Bustos, M., Havel, P. J., Moreno-Aliaga, M. J. Role of cardiotrophin-1 in the regulation of metabolic circadian rhythms and adipose core clock genes in mice and characterization of 24-h circulating CT-1 profiles in normal-weight and overweight/obese subjects.
Autores: Martínez-Fernández, L.; González-Muniesa, P; et al.
Revista: FASEB JOURNAL
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: Castilla, Rosa María; Barrenetxe, J.; et al.
Revista: FEBS JOURNAL
ISSN 1742-464X  Vol. 284  Nº Supl. 1  2017  págs. 157 - 158
Autores: Solas, Maite; Moreno-Aliaga MJ; et al.
Revista: BIOCHIMICA ET BIOPHYSICA ACTA
ISSN 0006-3002  Vol. 1862  Nº 4  2016  págs. 511 - 517
The concept of central insulin resistance and dysfunctional insulin signalling in sporadic Alzheimer's disease (AD) is now widely accepted and diabetes is recognized as one of the main risk factors for developing AD. Moreover, some lines of evidence indicated that VGlut1 is impaired in frontal regions of AD patients and this impairment is correlated with the progression of cognitive decline in AD. The present work hypothesizes that ketosis associated to insulin resistance could interfere with the normal activity of VGlut1 and its role in the release of glutamate in the hippocampus, which might ultimately lead to cognitive deficits. High fat diet (HFD) rats showed memory impairments and both peripheral (as shown by increased fasting plasma insulin levels and HOMA index) and hippocampal (as shown by decreased activation of insulin receptor, IRS-1 and pAkt) insulin pathway alterations, accompanied by increased ketone bodies production. All these effects were counteracted by ¿-lipoic acid (LA) administration. VGlut1 levels were significantly decreased in the hippocampus of HFD rats, and this decrease was reversed by LA. Altogether, the present results suggest that HFD induced alterations in central insulin signalling could switch metabolism to produce ketone bodies, which in turn, in the hippocampus, might lead to a decreased expression of VGlut1, and therefore to a decreased release of glutamate and hence, to the glutamatergic deficit described in AD. The ability of LA treatment to prevent the alterations in insulin signalling in this model of HFD might represent a possible new therapeutic target for the treatment of AD.
Autores: Prieto, Pedro Luis; Fernández, Marta; et al.
Revista: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
ISSN 1388-1981  Vol. 1861  Nº 3  2016  págs. 260 - 268
Chemerin is a novel adipokine associated with obesity and insulin resistance. Alpha-Lipoic acid (alpha-LA) has shown beneficial properties on diabetes and obesity. The aim of this study was to examine the effects of alpha-LA on chemerin production in adipocytes in absence or presence of TNF-alpha, insulin and AICAR. The potential signaling pathways involved in alpha-LA effects on chemerin were also analyzed. Alpha-LA actions on chemerin were tested in differentiated 3T3-L1 adipocytes and in some cases in human subcutaneous and omental adipocytes. Chemerin mRNA levels were measured by RT-PCR and the amount of chemerin secreted to culture media was determined by ELISA. Alpha-LA induced a concentration-dependent inhibition on both chemerin secretion and mRNA levels in 3T3-L1 adipocytes. The AMPK activator AICAR and the PI3K inhibitor LY294002 dramatically abrogated both chemerin secretion and gene expression, and further potentiated the inhibitory effect of alpha-LA on chemerin secretion. Insulin was able to partially reverse the inhibitory action of alpha-LA on chemerin secretion. Alpha-LA also reduced basal chemerin secretion in both subcutaneous and omental adipocytes from overweight/obese subjects. Moreover, alpha-LA was able to abolish the stimulatory effects of the pro-inflammatory cytokine TNF-alpha on chemerin secretion. Our data demonstrated the ability of alpha-LA to inhibit chemerin production, an adipokine associated to obesity and metabolic syndrome, suggesting that
Autores: Castilla, Rosa María; Lostao MP; et al.
Revista: ACTA PHYSIOLOGICA
ISSN 1748-1708  Vol. 217  Nº 3  2016  págs. 217 - 226
rCT-1 effects on ¿-Methyl-D-glucoside uptake were assessed in everted intestinal rings from wild-type and CT-1(-/-) mice and in Caco-2 cells. rCT-1 actions on SGLT-1 expression in brush border membrane vesicles and the identification of the potential signalling pathways involved were determined by Western blot. RESULTS: In vivo administration (0.2 mg kg(-1) ) of rCT-1 caused a significant decrease on ¿-Methyl-D-glucoside uptake in everted intestinal rings from wild-type and CT-1(-/-) mice after short-term and long-term treatments. Similarly, in vitro treatment (1-50 ng mL(-1) ) with rCT-1 reduced ¿-Methyl-D-glucoside uptake in everted intestinal rings. In Caco-2 cells, rCT-1 treatment (20 ng mL(-1) , 1 and 24 h) lowered apical uptake of ¿-Methyl-D-glucoside in parallel with a decrease on SGLT-1 protein expression. rCT-1 promoted the phosphorylation of STAT-3 after 5 and 15 min treatment, but inhibited the activation by phosphorylation of AMPK after 30 and 60 min. Interestingly, pre-treatment with the JAK/STAT inhibitor (AG490) and with the AMPK activator (AICAR) reversed the inhibitory effects of rCT-1 on ¿-Methyl-D-glucoside uptake. AICAR also prevented the inhibition of SGLT-1 observed in rCT-1-treated cells. CONCLUSIONS: CT-1 inhibits intestinal sugar absorption by the reduction of SGLT-1 levels through the AMPK pathway, which could also contribute to explain the hypoglycaemic and anti-obesity properties of CT-1.
Autores: Lorente, Silvia; Prieto, Pedro Luis; et al.
Revista: JOURNAL OF NUTRITIONAL BIOCHEMISTRY
ISSN 0955-2863  Vol. 37  2016  págs. 76 - 82
Eicosapentaenoic acid (EPA), a n-3 long-chain polyunsaturated fatty acid, has been reported to have beneficial effects in obesity-associated metabolic disorders. The objective of the present study was to determine the effects of EPA on the regulation of genes involved in lipid metabolism, and the ability of EPA to induce mitochondrial biogenesis and beiging in subcutaneous adipocytes from overweight subjects. Fully differentiated human subcutaneous adipocytes from overweight females (BMI: 28.1-29.8kg/m2) were treated with EPA (100-200 ¿M) for 24 h. Changes in mRNA expression levels of genes involved in lipogenesis, fatty acid oxidation and mitochondrial biogenesis were determined by qRT-PCR. Mitochondrial content was evaluated using MitoTracker® Green stain. The effects on peroxisome proliferator-activated receptor gamma, co-activator 1 alpha (PGC-1¿) and AMP-activated protein kinase (AMPK) were also characterized. EPA down-regulated lipogenic genes expression while up-regulated genes involved in fatty acid oxidation. Moreover, EPA-treated adipocytes showed increased mitochondrial content, accompanied by an up-regulation of nuclear respiratory factor-1, mitochondrial transcription factor A and cytochrome c oxidase IV mRNA expression. EPA also promoted the activation of master regulators of mitochondrial biogenesis such as sirtuin 1, PGC1-¿ and AMPK. In parallel, EPA induced the expression of genes that typify beige adipocytes such as fat determination factor PR domain containing 16, uncoupling protein 1 and cell death-inducing DFFA-like effector A, T-Box protein 1 and CD137. Our results suggest that EPA induces a remodeling of adipocyte metabolism preventing fat storage and promoting fatty acid oxidation, mitochondrial biogenesis and beige-like markers in human subcutaneous adipocytes from overweight subjects.
Autores: Milagro FI; Moreno-Aliaga MJ; Martínez, JA;
Revista: NEW ENGLAND JOURNAL OF MEDICINE
ISSN 0028-4793  Vol. 374  Nº 2  2016  págs. 190 - 191
Autores: Sáinz, Neira; González-Navarro, CJ; Martínez, JA; et al.
Revista: EXPERT OPINION ON THERAPEUTIC TARGETS
ISSN 1472-8222  Vol. 19  Nº 7  2015  págs. 893 - 909
Introduction: Leptin is a hormone with a key role in food intake and body weight homeostasis. Congenital leptin deficiency (CLD) is a rare disease that causes hyperphagia and early severe obesity. However, common obesity conditions are associated with hyperleptinemia and leptin resistance. Areas Covered: The main signaling pathways activated by leptin as well as the mechanisms underlying the regulatory actions of leptin on food intake and on lipid and glucose metabolism are reviewed. The potential mechanisms involving leptin resistance and the main regulatory hormonal and nutritional factors controlling leptin production/functions are also analyzed. The pathophysiology of leptin in human obesity, and especially the trials analyzing effects of leptin replacement therapy in patients with CLD or in subjects with common obesity and in post-obese weight-reduced subjects are also summarized. Expert Opinion: The use of drugs or specific bioactive food components with anti-inflammatory properties to reduce the inflammatory state associated with obesity, especially at the hypothalamus, may help to overcome leptin resistance. Research should also be focused on investigating dietary strategies, food supplements or drugs capable of avoiding or reversing the leptin fall during weight management, in order to promote sustained body weight lowering and weight loss maintenance.
Autores: Sáinz, Neira; Moreno-Aliaga MJ; et al.
Revista: METABOLISM-CLINICAL AND EXPERIMENTAL
ISSN 0026-0495  Vol. 64  Nº 1  2015  págs. 35 - 46
Obesity is a chronic disease that represents one of the most serious global health burdens associated to an excess of body fat resulting from an imbalance between energy intake and expenditure, which is regulated by environmental and genetic interactions. The adipose-derived hormone leptin acts via a specific receptor in the brain to regulate energy balance and body weight, although this protein can also elicit a myriad of actions in peripheral tissues. Obese individuals, rather than be leptin deficient, have in most cases, high levels of circulating leptin. The failure of these high levels to control body weight suggests the presence of a resistance process to the hormone that could be partly responsible of disturbances on body weight regulation. Furthermore, leptin resistance can impair physiological peripheral functions of leptin such as lipid and carbohydrate metabolism and nutrient intestinal utilization. The present document summarizes those findings regarding leptin resistance development and the role of this hormone in the development and maintenance of an obese state. Thus, we focused on the effect of the impaired leptin action on adipose tissue, liver, skeletal muscle and intestinal function and the accompanying relationships with diet-induced obesity. The involvement of some inflammatory mediators implicated in the development of obesity and their roles in leptin resistance development are also discussed.
Autores: Lorente, Silvia; Navas-Carretero, Santiago; et al.
Revista: JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
ISSN 1138-7548  Vol. 71  Nº 2  2015  págs. 341 - 349
Inflammation is involved in the pathophysiology of many chronic diseases, such as rheumatoid arthritis and neurodegenerative diseases. Several studies have evidenced important anti-inflammatory and immunomodulatory properties of omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs). This review illustrates current knowledge about the efficacy of n-3 LC-PUFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), particularly) in preventing and/or treating several chronic inflammatory conditions (inflammatory bowel diseases and rheumatoid arthritis) as well as their potential benefits on neurodegenerative diseases. It is well established that n-3 LC-PUFAs are substrates for synthesis of novel series of lipid mediators (e.g., resolvins, protectins, and maresins) with potent anti-inflammatory and pro-resolving properties, which have been proposed to partly mediate the protective and beneficial actions of n-3 LC-PUFAs. Here, we briefly summarize current knowledge from preclinical studies analyzing the actions of EPA- and DHA-derived resolvins and protectins on pathophysiological models of rheumatoid arthritis, Alzheimer, and irritable bowel syndrome.
Autores: Martínez-Fernández, L.; Huerta, A. E.; et al.
Revista: PROSTAGLANDINS AND OTHER LIPID MEDIATORS
ISSN 1098-8823  Vol. 121  Nº Part A  2015  págs. 24 - 41
The n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) have been reported to improve obesity-associated metabolic disorders including chronic inflammation, insulin resistance and dyslipidaemia. Growing evidence exits about adipose tissue as a target in mediating the beneficial effects of these marine n-3 PUFAs in adverse metabolic syndrome manifestations. Therefore, in this manuscript we focus in reviewing the current knowledge about effects of marine n-3 PUFAs on adipose tissue metabolism and secretory functions. This scope includes n-3 PUFAs actions on adipogenesis, lipogenesis and lipolysis as well as on fatty acid oxidation and mitochondrial biogenesis. The effects of n-3 PUFAs on adipose tissue glucose uptake and insulin signaling are also summarized. Moreover, the roles of peroxisome proliferator-activated receptor ¿ (PPAR¿) and AMPK activation in mediating n-3 PUFAs actions on adipose tissue functions are discussed. Finally, the mechanisms underlying the ability of n-3 PUFAs to prevent and/or ameliorate adipose tissue inflammation are also revised, focusing on the role of n-3 PUFAs-derived specialized proresolving lipid mediators such as resolvins, protectins and maresins.
Autores: Prieto, Pedro Luis; Pardo, V.; et al.
Revista: FREE RADICAL BIOLOGY AND MEDICINE
ISSN 0891-5849  Vol. 84  2015  págs. 263 - 278
Excess of saturated free fatty acids, such as palmitic acid (PA), in hepatocytes has been implicated in nonalcoholic fatty liver disease. ¿-Lipoic acid (LA) is an antioxidant that protects against oxidative stress conditions. We have investigated the effects of LA in the early activation of oxidative and endoplasmic reticulum stress, lipid accumulation, and Nrf2-mediated antioxidant defenses in hepatocytes treated with PA or in rats fed a high-fat diet. In primary human hepatocytes, a lipotoxic concentration of PA triggered endoplasmic reticulum stress, induced the apoptotic transcription factor CHOP, and increased the percentage of apoptotic cells. Cotreatment with LA prevented these effects. Similar results were found in mouse hepatocytes in which LA attenuated PA-mediated activation of caspase 3 and reduced lipid accumulation by decreasing PA uptake and increasing fatty acid oxidation and lipophagy, thereby preventing lipoapoptosis. Moreover, LA augmented the proliferation capacity of hepatocytes after PA challenge. Antioxidant effects of LA ameliorated reactive oxygen species production and endoplasmic reticulum stress and protected against mitochondrial apoptosis in hepatocytes treated with PA. Cotreatment with PA and LA induced an early nuclear translocation of Nrf2 and activated antioxidant enzymes, whereas reduction of Nrf2 by siRNA abolished the benefit of LA on PA-induced lipoapoptosis. Importantly, posttreatment with LA reversed the established damage induced by PA in hepatocytes, as well as preventing obesity-induced oxidative stress and lipoapoptosis in rat liver. In conclusion, our work has revealed that in hepatocytes, Nrf2 is an essential early player in the rescue of oxidative stress by LA leading to protection against PA-mediated lipoapoptosis.
Autores: Huerta, Ana Elsa; Navas-Carretero, Santiago; Prieto, Pedro Luis; et al.
Revista: OBESITY
ISSN 1930-7381  Vol. 23  Nº 2  2015  págs. 313 - 321
Objective To evaluate the potential body weight-lowering effects of dietary supplementation with eicosapentaenoic acid (EPA) and ¿-lipoic acid separately or combined in healthy overweight/obese women following a hypocaloric diet. Methods This is a short-term double-blind placebo-controlled study with parallel design that lasted 10 weeks. Of the randomized participants, 97 women received the allocated treatment [Control, EPA (1.3 g/d), ¿-lipoic acid (0.3 g/d), and EPA¿+¿¿-lipoic acid (1.3 g/d¿+¿0.3 g/d)], and 77 volunteers completed the study. All groups followed an energy-restricted diet of 30% less than total energy expenditure. Body weight, anthropometric measurements, body composition, resting energy expenditure, blood pressure, serum glucose, and insulin and lipid profile, as well as leptin and ghrelin levels, were assessed at baseline and after nutritional intervention. Results Body weight loss was significantly higher (P¿<¿0.05) in those groups supplemented with ¿-lipoic acid. EPA supplementation significantly attenuated (P¿<¿0.001) the decrease in leptin levels that occurs during weight loss. Body weight loss improved lipid and glucose metabolism parameters but without significant differences between groups. Conclusions The intervention suggests that ¿-lipoic acid supplementation alone or in combination with EPA may help to promote body weight loss in healthy overweight/obese women following energy-restricted diets.
Autores: Mansego, Maria L; Milagro FI; Zulet, María de los Ángeles; et al.
Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN 1422-0067  Vol. 16  Nº 8  2015  págs. 16816 - 16832
The aim of this study was to evaluate whether genome-wide levels of DNA methylation are associated with age and the health risks of obesity (HRO); defined according to BMI categories as "Low HRO" (overweight and class 1 obesity) versus "High HRO" (class 2 and class 3 obesity). Anthropometric measurements were assessed in a subsample of 48 volunteers from the Metabolic Syndrome Reduction in Navarra (RESMENA) study and 24 women from another independent study, Effects of Lipoic Acid and Eicosapentaenoic Acid in Human Obesity (OBEPALIP study). In the pooled population; the methylation levels of 55 CpG sites were significantly associated with age after Benjamini-Hochberg correction. In addition, DNA methylation of three CpG sites located in ELOVL2; HOXC4 and PI4KB were further negatively associated with their mRNA levels. Although no differentially methylated CpG sites were identified in relation to HRO after multiple testing correction; several nominally significant CpG sites were identified in genes related to insulin signaling; energy and lipid metabolism. Moreover, statistically significant associations between BMI or mRNA levels and two HRO-related CpG sites located in GPR133 and ITGB5 are reported. As a conclusion, these findings from two Spanish cohorts add knowledge about the important role of DNA methylation in the age-related regulation of gene expression. In addition; a relevant influence of age on DNA methylation in white blood cells was found, as well as, on a trend level, novel associations between DNA methylation and obesity.
Autores: Huerta, Ana Elsa; Prieto, Pedro Luis; Fernández, Marta; et al.
Revista: JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
ISSN 1138-7548  Vol. 71  Nº 3  2015  págs. 547 - 558
Irisin is a myokine/adipokine with potential role in obesity and diabetes. The objectives of the present study were to analyse the relationship between irisin and glucose metabolism at baseline and during an oral glucose tolerance test (OGTT) and to determine the effects of eicosapentaenoic acid (EPA) and/or alpha-lipoic acid treatment on irisin production in cultured human adipocytes and in vivo in healthy overweight/obese women following a weight loss program. Seventy-three overweight/obese women followed a 30 % energy-restricted diet supplemented without (control) or with EPA (1.3 g/day), alpha-lipoic acid (0.3 g/day) or both EPA + alpha-lipoic acid (1.3 + 0.3 g/day) during 10 weeks. An OGTT was performed at baseline. Moreover, human adipocytes were treated with EPA (100-200 mu M) or alpha-lipoic acid (100-250 mu M) during 24 h. At baseline plasma, irisin circulating levels were positively associated with glucose levels; however, serum irisin concentrations were not affected by the increment in blood glucose or insulin during the OGTT. Treatment with alpha-lipoic acid (250 mu M) upregulated Fndc5 messenger RNA (mRNA) and irisin secretion in cultured adipocytes. In overweight/obese women, irisin circulating levels decreased significantly after weight loss in all groups, while no additional differences were induced by EPA or alpha-lipoic acid supplementation. Moreover, plasma irisin levels were positively associated with higher glucose concentrations at beginning and at endp
Autores: Fernández, Marta; Prieto, Pedro Luis; et al.
Revista: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
ISSN 1388-1981  Vol. 1851  Nº 3  2015  págs. 273 - 281
Alpha-Lipoic acid (¿-Lip) is a natural occurring antioxidant with beneficial anti-obesity properties. The aim of this study was to investigate the putative effects of alpha-Lip on mitochondrial biogenesis and the acquirement of brown-like characteristics by subcutaneous adipocytes from overweight/obese subjects. Thus, fully differentiated human subcutaneous adipocytes were treated with alpha-Lip (100 and 250 ¿M) for 24 h for studies on mitochondrial content and morphology, mitochondrial DNA (mtDNA) copy number, fatty acid oxidation enzymes and brown/beige characteristic genes. The involvement of the Sirtuin1/Peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (SIRT1/PGC-1alpha) pathway was also evaluated. Our results showed that alpha-Lip increased mitochondrial content in cultured human adipocytes as revealed by electron microscopy and by mitotracker green labeling. Moreover, an enhancement in mtDNA content was observed. This increase was accompanied by an up-regulation of SIRT1 protein levels, a decrease in PGC-1alpha acetylation and up-regulation of Nuclear respiratory factor 1 (Nrf1) and Mitochondrial transcription factor (Tfam) transcription factors. Enhanced oxygen consumption and fatty acid oxidation enzymes, Carnitine palmitoyl transferase 1 and Acyl-coenzyme A oxidase (CPT-1 and ACOX) were also observed. Mitochondria from alpha-Lip-treated adipocytes exhibited some morphological characteristics of brown mitochondria, and alpha-Lip also induced up-regulation of some brown/beige adipocytes markers such as cell death-inducing DFFA-like effector a (Cidea) and T-box 1 (Tbx1). Moreover, alpha-Lip up-regulated PR domain containing 16 (Prdm16) mRNA levels in treated adipocytes. Therefore, our study suggests the ability of alpha-Lip to promote mitochondrial biogenesis and brown-like remodeling in cultured white subcutaneous adipocytes from overweight/obese donors.
Autores: Fernández, Marta; Laiglesia, L. M.; et al.
Revista: JOURNAL OF LIPID RESEARCH
ISSN 0022-2275  Vol. 55  Nº 12  2014  págs. 2634 - 2643
Cardiotrophin-1 (CT-1) is a cytokine with antiobesity properties and with a role in lipid metabolism regulation and adipose tissue function. The aim of this study was to analyze the molecular mechanisms involved in the lipolytic actions of CT-1 in adipocytes. Recombinant CT-1 (rCT-1) effects on the main proteins and signaling pathways involved in the regulation of lipolysis were evaluated in 3T3-L1 adipocytes and in mice. rCT-1 treatment stimulated basal glycerol release in a concentration- and time-dependent manner in 3T3-L1 adipocytes. rCT-1 (20 ng/ml for 24 h) raised cAMP levels, and in parallel increased protein kinase (PK)A-mediated phosphorylation of perilipin and hormone sensitive lipase (HSL) at Ser660. siRNA knock-down of HSL or PKA, as well as pretreatment with the PKA inhibitor H89, blunted the CT-1-induced lipolysis, suggesting that the lipolytic action of CT-1 in adipocytes is mainly mediated by activation of HSL through the PKA pathway. In ob/ob mice, acute rCT-1 treatment also promoted PKA-mediated phosphorylation of perilipin and HSL at Ser660 and Ser563, and increased adipose triglyceride lipase (desnutrin) content in adipose tissue. These results showed that the ability of CT-1 to regulate the activity of the main lipases underlies the lipolytic action of this cytokine in vitro and in vivo, and could contribute to CT-1 antiobesity effects.
Autores: Fernández, Marta; Prieto, Pedro Luis; et al.
Revista: OBESITY
ISSN 1930-7381  Vol. 22  Nº 10  2014  págs. 2210 - 2215
OBJECTIVE: alfa-Lipoic acid (alfa-LA) is a natural occurring antioxidant with beneficial effects on obesity. The aim of this study was to investigate the putative effects of alfa-LA on triglyceride accumulation and lipogenesis in subcutaneous adipocytes from overweight/obese subjects and to determine the potential mechanisms involved. METHODS: Fully differentiated human subcutaneous adipocytes were treated with alfa-LA (100 and 250 µM) during 24 h for studying triglyceride content, de novo lipogenesis, and levels of key lipogenic enzymes. The involvement of AMP-activated protein kinase (AMPK) activation was also evaluated. RESULTS: alfa-LA down-regulated triglyceride content by inhibiting fatty acid esterification and de novo lipogenesis. These effects were mediated by reduction in fatty acid synthase (FAS), stearoyl-coenzyme A desaturase 1, and diacylglycerol O-acyltransferase 1 protein levels. Interestingly, alfa-LA increased AMPK and acetyl CoA carboxylase phosphorylation, while the presence of the AMPK inhibitor Compound C reversed the inhibition observed on FAS protein levels. CONCLUSIONS: alfa-LA down-regulates key lipogenic enzymes, inhibiting lipogenesis and reducing triglyceride accumulation through the activation of AMPK signaling pathway in human subcutaneous adipocytes from overweight/obese subjects.
Autores: Lorente, Silvia; Navas-Carretero, Santiago; et al.
Revista: JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
ISSN 1138-7548  Vol. 69  Nº 3  2013  págs. 633 - 651
The present review aims to illustrate current knowledge about the efficacy of omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) in treating/preventing several metabolic pathologies. We reviewed systematically the published evidence on the effectiveness of n-3 LC-PUFAs fish consumption or n-3 LC-PUFAs supplementation on prevention/treatment of obesity, metabolic syndrome, and cardiovascular diseases. Most of the reviewed studies were randomized-controlled interventional trials, although some relevant prospective and cross-sectional studies as well as some meta-analysis were also reviewed. Supplementation with n-3 LC-PUFAs might improve some obesity-associated metabolic syndrome features such as insulin resistance, hypertension and dyslipidemia by decreasing plasma triglycerides. Moreover, the blood pressure-lowering and anti-inflammatory properties of these fatty acids and their benefits in vascular function might confer cardioprotection. However, the efficacy of n-3 LC-PUFA on reducing myocardial infarction, arrhythmia, cardiac and sudden death, or stroke is controversial. Due to the beneficial actions of n-3 LC-PUFAs, several worldwide government and health organizations have established some recommendations of n-3 LC-PUFAs intake for groups of population. In general, the recommended levels for diseases prevention are lower than those advised for particular treatments. However, more clinical trials are necessary to recommend the most effective dosages and formulas (type of n-3 LC-PUFA, EPA/DHA ratio) for specific pathologies.
Autores: Fernández, Marta; Prieto, Pedro Luis; Martínez, JA; et al.
Revista: CLINICAL LIPIDOLOGY
ISSN 1758-4299  Vol. 8  Nº 3  2013  págs. 371 - 383
The incidence of obesity is increasing worldwide and concerns about its association with comorbidities such as cardiovascular disease or Type 2 diabetes led to research into alternative therapies to modulate bodyweight and adiposity. alpha-lipoic acid is a natural antioxidant with potential beneficial effects on obesity and its related disorders. This article aims to review the evidence from animal studies, with particular reference to trials in humans. Moreover, the putative mechanisms mediating the antiobesity properties of alpha-lipoic acid, including inhibition of food intake, stimulation of energy expenditure, increase of mitochondrial biogenesis, inhibition of lipogenesis and promotion of fat oxidation, among others, will be evaluated.
Autores: Prieto, Pedro Luis; Fernández, Marta; et al.
Revista: JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
ISSN 1138-7548  Vol. 69  Nº 3  2013  págs. 595 - 600
Lipoic acid (LA) is a naturally occurring compound with antioxidant properties. Recent attention has been focused on the potential beneficial effects of LA on obesity and related metabolic disorders. Dietary supplementation with LA prevents insulin resistance and upregulates adiponectin, an insulin-sensitizing adipokine, in obese rodents. The aim of this study was to investigate the direct effects of LA on adiponectin production in cultured adipocytes, as well as the potential signaling pathways involved. For this purpose, fully differentiated 3T3-L1 adipocytes were treated with LA (1-500 ¿M) during 24 h. The amount of adiponectin secreted to media was detected by ELISA, while adiponectin mRNA expression was determined by RT-PCR. Treatment with LA induced a dose-dependent inhibition on adiponectin gene expression and protein secretion. Pretreatment with the PI3K inhibitor LY294002 inhibited adiponectin secretion and mRNA levels, and significantly potentiated the inhibitory effect of LA on adiponectin secretion. The AMPK activator AICAR also reduced adiponectin production, but surprisingly, it was able to reverse the LA-induced inhibition of adiponectin. The JNK inhibitor SP600125 and the MAPK inhibitor PD98059 did not modify the inhibitory effect of LA on adiponectin. In conclusion, our results revealed that LA reduces adiponectin secretion in 3T3-L1 adipocytes, which contrasts with the stimulation of adiponectin described after in vivo supplementation with LA, suggesting that an indirect mechanism or some in vivo metabolic processing is involved.
Autores: Prieto, Pedro Luis; Fernández, Marta; et al.
Revista: European Journal of Nutrition
ISSN 1436-6207  Vol. 52  Nº 2  2013  págs. 779 - 787
Lipoic acid (LA) is an antioxidant with antiobesity and antidiabetic properties. Adiponectin is an adipokine with potent anti-inflammatory and insulin-sensitizing properties. AMP-activated protein kinase (AMPK) is a key enzyme involved in cellular energy homeostasis. Activation of AMPK has been considered as a target to reverse the metabolic abnormalities associated with obesity and type 2 diabetes. The aim of this study was to determine the effects of LA on AMPK phosphorylation and adiponectin production in adipose tissue of low-fat (control diet) and high-fat diet-fed rats. Dietary supplementation with LA reduced body weight and adiposity in control and high-fat-fed rats. LA also reduced basal hyperinsulinemia as well as the homeostasis model assessment (HOMA) levels, an index of insulin resistance, in high-fat-fed rats, which was in part independent of their food intake lowering actions. Furthermore, AMPK phosphorylation was increased in white adipose tissue (WAT) from LA-treated rats as compared with pair-fed animals. Dietary supplementation with LA also upregulated adiponectin gene expression in WAT, while a negative correlation between adiposity-corrected adiponectin levels and HOMA index was found. Our present data suggest that the ability of LA supplementation to prevent insulin resistance in high-fat diet-fed rats might be related in part to the stimulation of AMPK and adiponectin in WAT.
Autores: Chueca M; et al.
Revista: METABOLISM-CLINICAL AND EXPERIMENTAL
ISSN 0026-0495  Vol. 62  Nº 10  2013  págs. 1429 - 1436
OBJECTIVE: Cardiotrophin-1 (CT-1) shares some similarities with other cytokines, and participates in the control of energy metabolism. Higher circulating levels are observed in obese humans, but little information is gathered in weight loss (WL) programs. Therefore, we aimed to investigate the association of serum CT-1 levels with metabolic variables and the risk of developing metabolic syndrome (MetS) after a WL program in overweight/obese children. SUBJECTS AND METHODS: Forty-four overweight/obese children (mean age 11.5y; 50% males) undergoing a 10-week WL program were enrolled. Subjects were dichotomized at the median of Body Mass Index-Standard Deviation Score (BMI-SDS) change, as high and low responders after intervention. RESULTS: CT-1 levels were significantly reduced (-48 fmol/mL, p=0.043) in the high responder group after the WL program. They had significantly lower body weight (-3.7kg, p<0.001), body fat mass (-8%, p<0.001), BMI-SDS (-0.78, p<0.001) and waist circumference (-5.4cm, p<0.001), and a significant improvement in lipid and glucose profiles (p<0.05). Interestingly, decreased CT-1 levels significantly predicted changes in total cholesterol (41%) and LDL-cholesterol (28%). Moreover, in our participants the lower the CT-1 levels, the higher the reduction in MetS risk components, after the 10-week intervention, (p-ANCOVA=0.040, p-trend=0.024). CONCLUSION: We showed, for the first time, a reduction in serum CT-1 levels after a WL program and this decrease in CT-1 was strongly associated with a reduction in cholesterol levels and in MetS risk factors in overweight/obese children. Our findings may suggest that CT-1 could be an indirect marker for the diagnosis of MetS in this population.
Autores: González-Muniesa, P; Marrades, María Pilar; Martínez, JA; et al.
Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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, P; Fernández, Marta; Prieto, Pedro Luis; et al.
Revista: OBESITY FACTS
ISSN 1662-4025  Vol. 6  Nº Supl. 1  2013  págs. 52
Autores: González-Muniesa, P; Martínez, JA; et al.
Revista: OBESITY FACTS
ISSN 1662-4025  Vol. 6  Nº Suppl. 1  2013  págs. 71
Autores: Alves NEG; Valdés, SE; Silveira CMM; et al.
Revista: THE OPEN NUTRACEUTICALS JOURNAL
ISSN 1876-3960  Vol. 5  2012  págs. 193 - 206
Obesity is recognised as a condition of low-grade chronic inflammation resulting from macrophage infiltration of adipose tissue and activation of inflammatory pathways by oxidative stress mechanisms that lead to the development of insulin resistance. Various natural bioactive compounds (NBCs) with anti-inflammatory and anti-oxidant effects may im-prove adipocyte dysfunction associated with metabolic syndrome. The present review focuses on the effects of phenolic compounds, n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and lipoic acid (LA) on the pathophysiological mechanisms of obesity. In this review, a total of 120 studies were included, and data thus obtained reflect beneficial physiological effects of n-3 LC-PUFA, LA and different phenolic compounds, including kaempferol, luteolin, apigenin, quercetin, resveratrol, curcumin, catechins, phenolic acids, in the prevention and/or attenuation of metabolic disturbances associated with obesity. Additionally, information from clinical studies provides new insights for defining the dose-response relationship of dietary compounds, necessary time of exposure and potential side effects of these NBCs in the treatment of obesity and indicates further study is needed to verify these relationships.
Autores: González-Muniesa, P; 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: Moreno-Aliaga MJ; Romero-Lozano, M. A.; Prieto, Jesús María;
Revista: ADIPOCYTE
ISSN 2162-3945  Vol. 1  Nº 2  2012  págs. 112 - 115
Cardiotrophin-1 (CT-1) is a member of the gp130 family of cytokines. In a recent study we examined the metabolic features of ct-1 null mice and the effects on body composition, glucose and lipid metabolism of acute and chronic administration of recombinant CT-1. Our data revealed that CT-1 is a key regulator of energy metabolism with potential applications in the treatment of obesity and the metabolic syndrome. This commentary discusses the significance of these findings in the context of other key studies in the field of obesity and insulin resistance.
Autores: Lorente, Silvia; Marti A; Fernández, Marta; et al.
Revista: The Journal of Nutritional Biochemistry
ISSN 0955-2863  Vol. 23  Nº 3  2012  págs. 218-227
Autores: Fernández, Marta; Prieto, Pedro Luis; et al.
Revista: JOURNAL OF LIPID RESEARCH
ISSN 0022-2275  Vol. 53  Nº 11  2012  págs. 2296 - 2306
Lipoic acid ( LA) is a naturally occurring compound with beneficial effects on obesity. The aim of this study was to evaluate its effects on lipolysis in 3T3-L1 adipocytes and the mechanisms involved. Our results revealed that LA induced a dose- and time-dependent lipolytic action, which was reversed by pretreatment with the c-Jun N-terminal kinase inhibitor SP600125, the PKA inhibitor H89, and the AMP-activated protein kinase activator AICAR. In contrast, the PI3K/Akt inhibitor LY294002 and the PDE3B antagonist cilostamide enhanced LA-induced lipolysis. LA treatment for 1 h did not modify total protein content of hormone-sensitive lipase (HSL) but significantly increased the phosphorylation of HSL at Ser(563) and at Ser(660), which was reversed by H89. LA treatment also induced a marked increase in PKA-mediated perilipin phosphorylation. LA did not significantly modify the protein levels of adipose triglyceride lipase or its activator comparative gene identification 58 ( CGI-58) and inhibitor G(0)/G(1) switch gene 2 (G0S2). Furthermore, LA caused a significant inhibition of adipose-specific phospholipase A2 (AdPLA) protein and mRNA levels in parallel with a decrease in the amount of prostaglandin E-2 released and an increase in cAMP content. Together, these data suggest that the lipolytic actions of LA are mainly mediated by phosphorylation of HSL through cAMP-mediated activation of protein kinase A probably through the inhibition of AdPLA and prostaglandin E-2.
Autores: García, Diego Fernando; Campión, Francisco Javier; Arellano, AV; et al.
Revista: EXPERIMENTAL BIOLOGY AND MEDICINE
ISSN 1535-3702  Vol. 237  Nº 4  2012  págs. 407 - 416
Autores: González-Muniesa, P; et al.
Revista: JOURNAL OF NUTRITIONAL BIOCHEMISTRY
ISSN 0955-2863  Vol. 23  Nº 12  2012  págs. 1676 - 1684
Autores: Prieto, Pedro Luis; Barraco, G. M.; Martínez, JA; et al.
Revista: NUTRICION HOSPITALARIA
ISSN 0212-1611  Vol. 27  Nº 5  2012  págs. 22
Autores: Prieto, Pedro Luis; Barraco, G. M.; Martínez, JA; et al.
Revista: OBESITY FACTS
ISSN 1662-4025  Vol. 5  Nº Suppl. 1  2012  págs. 158 - 159
Autores: Moreno-Aliaga MJ; et al.
Revista: CELL METABOLISM
ISSN 1550-4131  Vol. 14  Nº 2  2011  págs. 242 - 253
Cardiotrophin-1 (CT-1) is a member of the gp130 family of cytokines. We observed that ct-1¿/¿ mice develop mature-onset obesity, insulin resistance, and hypercholesterolemia despite reduced calorie intake. Decreased energy expenditure preceded and accompanied the development of obesity. Acute treatment with rCT-1 decreased blood glucose in an insulin-independent manner and increased insulin-stimulated AKT phosphorylation in muscle. These changes were associated with stimulation of fatty acid oxidation, an effect that was absent in AMPK¿2¿/¿ mice. Chronic rCT-1 treatment reduced food intake, enhanced energy expenditure, and induced white adipose tissue remodeling characterized by upregulation of genes implicated in the control of lipolysis, fatty acid oxidation, and mitochondrial biogenesis and genes typifying brown fat phenotype. Moreover, rCT-1 reduced body weight and corrected insulin resistance in ob/ob and in high-fat-fed obese mice. We conclude that CT-1 is a master regulator of fat and glucose metabolism with potential applications for treatment of obesity and insulin resistance.
Autores: García, Diego Fernando; Arellano, AV; Milagro FI; et al.
Revista: Journal of physiology and biochemistry
ISSN 1138-7548  Vol. 67  Nº 3  2011  págs. 453 - 461
Autores: Prieto, Pedro Luis; Fernández, Marta; et al.
Revista: BIOCHIMICA ET BIOPHYSICA ACTA
ISSN 0006-3002  Vol. 1807  Nº 6  2011  págs. 664 - 678
Obesity is a complex disease caused by the interaction of a myriad of genetic, dietary, lifestyle and environmental factors, which favors a chronic positive energy balance, leading to increased body fat mass. There is emerging evidence of a strong association between obesity and an increased risk of cancer. However, the mechanisms linking both diseases are not fully understood. Here, we analyze the current knowledge about the potential contribution that expanding adipose tissue in obesity could make to the development of cancer via dysregulated secretion of pro-inflammatory cytokines, chemokines and adipokines such as TNF-¿, IL-6, leptin, adiponectin, visfatin and PAI-1. Dietary factors play an important role in the risk of suffering obesity and cancer. The identification of bioactive dietary factors or substances that affect some of the components of energy balance to prevent/reduce weight gain as well as cancer is a promising avenue of research. This article reviews the beneficial effects of some bioactive food molecules (n-3 PUFA, CLA, resveratrol and lipoic acid) in energy metabolism and cancer, focusing on the molecular mechanisms involved, which may provide new therapeutic targets in obesity and cancer.
Autores: Fernández, Marta; Prieto, Pedro Luis; et al.
Revista: Journal of physiology and biochemistry
ISSN 1138-7548  Vol. 67  Nº 3  2011  págs. 479 - 486
Lipoic acid (LA) is an antioxidant with therapeutic properties on several diseases like diabetes and obesity. Apelin is a novel adipokine with potential beneficial actions on glucose metabolism and insulin resistance. The aim of this study was to examine in 3T3-L1 adipocytes the effects of LA on apelin gene expression and secretion, as well as elucidate the signaling pathways involved. We also tested the regulation of adipose apelin gene expression by LA supplementation in a model of high-fat diet-induced obesity. LA increased apelin secretion but not apelin gene expression in 3T3-L1 adipocytes. The AMPK inhibitor Compound C induced an increase in LA-stimulated apelin production, and, on the contrary, the AMPK activator AICAR completely reversed the LA stimulatory effects on apelin secretion, also inducing a significant reduction in apelin mRNA levels in this in vitro model. Apelin mRNA levels were increased in those animals fed with the high-fat diet, while the caloric restriction decreased apelin mRNA to control levels. However, apelin gene expression was not significantly modified in rats treated with LA compared with the obese group. The current data suggest the ability of LA to modulate apelin secretion by adipocytes. However the insulin-sensitizing effect of LA in vivo is not related to changes in apelin gene expression in our model of diet-induced obesity.
Autores: Prieto, Pedro Luis; et al.
Revista: Biomarkers
ISSN 1354-750X  Vol. 16  Nº 8  2011  págs. 670 - 678
The need for minimally invasive biomarkers to predict the progression of non-alcoholic fatty liver disease to non-alcoholic steatohepatitis is a priority. Oxidative stress and mitochondrial dysfunction contribute in this physiopathological process. The aim of this study was to analyze the potential role of erythrocytes as surrogate biomarkers of hepatic mitochondrial oxidative status in an animal model under different dietary oxidative conditions. Interestingly, we found that erythrocyte antioxidant status correlated with triglyceride content (p¿<¿0.05-p¿<¿0.001), thiobarbituric acid reactive species levels (p¿<¿0.001) and with liver mitochondrial antioxidant levels (p¿<¿0.001). These data suggest that erythrocyte antioxidant defenses could be used as sensitive and minimally invasive biomarkers of mitochondrial status in diverse oxidative conditions.
Autores: Moreno-Aliaga MJ; Prieto, Jesús María;
Revista: AGING-US
ISSN 1945-4589  Vol. 3  Nº 8  2011  págs. 698 - 699
Autores: Marrades, María Pilar; González-Muniesa, P; Arteta, David; et al.
Revista: JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
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: García, Diego Fernando; Campión, Francisco Javier; et al.
Revista: Mol Nutr Food Res
ISSN 1613-4125  Vol. 55  2011  págs. 257 - 263
Autores: Prieto, Pedro Luis; Fernández, Marta; et al.
Revista: MOLECULAR NUTRITION AND FOOD RESEARCH
ISSN 1613-4125  Vol. 55  Nº 7  2011  págs. 1059 - 1069
Scope: Lipoic acid (LA) is an antioxidant with therapeutic potential on several diseases such as diabetes and obesity. Hyperleptinemia and oxidative stress play a major role in the development of obesity-linked diseases. The aim of this study was to examine in vivo and in vitro the effects of LA on leptin production, as well as to elucidate the mechanisms and signalling pathways involved in LA actions. Methods and results: Dietary supplementation with LA decreased both circulating leptin, and adipose tissue leptin mRNA in rats. Treatment of 3T3-L1 adipocytes with LA caused a concentration-dependent inhibition of leptin secretion and gene expression. Moreover, LA stimulated the anaerobic utilization of glucose to lactate, which negatively correlated with leptin secretion. Furthermore, LA enhanced phosphorylation of Sp1 and inhibited Sp1 transcriptional activity in 3T3-L1 adipocytes. Moreover, LA inhibited Akt phosphorylation, a downstream target of phosphatidylinositol 3-kinase (PI3K). Treatment with the PI3K inhibitor LY294002 mimicked LA actions, dramatically inhibiting both leptin secretion and gene expression and stimulating Sp1 phosphorylation. Conclusion: All of these data suggest that the phosphorylation of Sp1 and the accompanying reduced DNA-binding activity are likely to be involved in the inhibition of leptin induced by LA, which could be mediated in part by the abrogation of the PI3K/Akt pathway.
Autores: Fernández, Marta; Prieto, Pedro Luis; et al.
Revista: Annals of Nutrition and Metabolism
ISSN 0250-6807  Vol. 58  Nº Supl. 3  2011  págs. 379 - 379
Autores: Martínez de Lapiscina, Idoia; et al.
Revista: Annals of Nutrition and Metabolism
ISSN 0250-6807  Vol. 58  Nº Supl. 3  2011  págs. 262 - 263
Autores: García, Diego Fernando; Campión, Francisco Javier; Milagro FI; et al.
Revista: JOURNAL OF MOLECULAR ENDOCRINOLOGY
ISSN 0952-5041  Vol. 45  Nº 1  2010  págs. 33 - 43
Autores: Moreno-Aliaga MJ; Lorente, Silvia; Martínez, JA;
Revista: Proceedings of the Nutrition Society
ISSN 0029-6651  Vol. 69  Nº 3  2010  págs. 324 - 332
Obesity leads to several chronic morbidities including type 2 diabetes, dyslipidaemia, atherosclerosis and hypertension, which are major components of the metabolic syndrome. White adipose tissue (WAT) metabolism and WAT-derived factors (fatty acids and adipokines) play an important role in the development of these metabolic disturbances. In fact, dysregulated adipokine secretion from the expanded WAT of obese individuals contributes to the development of systemic low-grade inflammation, insulin resistance and metabolic syndrome. The n-3 PUFA EPA and DHA have been widely reported to have protective effects in a range of chronic inflammatory conditions including obesity. In fact, n-3 PUFA have been shown to ameliorate low-grade inflammation in adipose tissue associated with obesity and up-regulate mitochondrial biogenesis and induce beta-oxidation in WAT in mice. Moreover, the ability of n-3 PUFA to regulate adipokine gene expression and secretion has been observed both in vitro and in vivo in rodents and human subjects. The present article reviews: (1) the physiological role of adiponectin, leptin and pre-B cell colony-enhancer factor/visfatin, three adipokines with immune-modulatory properties involved in the regulation of metabolism and insulin sensitivity and (2) the actions of n-3 PUFA on these adipokines focusing on the underlying mechanisms and the potential relationship with the beneficial effects of these fatty acids on obesity-associated metabolic disorders. It can be concluded that the ability of n-3 PUFA to improve obesity and insulin resistance conditions partially results from the modulation of WAT metabolism and the secretion of bioactive adipokines including leptin, adiponectin and visfatin.
Autores: Lorente, Silvia; Marti A; Martínez, JA; et al.
Revista: MOLECULAR NUTRITION AND FOOD RESEARCH
ISSN 1613-4125  Vol. 54  Nº Suppl. 1  2010  págs. S104 - S111
Recent studies have shown the ability of apelin to restore glucose tolerance in obese and insulin-resistant mice. Eicosapentaenoic acid (EPA) is a polyunsaturated fatty acid (PUFA) from the omega-3 family that has many beneficial effects in obesity-linked disorders. The aim of this study was to examine in vitro the effects of EPA on apelin secretion and gene expression in mature 3T3-L1 adipocytes. Treatment with EPA (100 and 200 mu M) significantly increased basal (p<0.01) and insulin-stimulated (p<0.001) apelin secretion and gene expression in adipocytes. EPA also stimulated Akt phosphorylation, a down-stream target of phosphatidylinositol 3-kinase (PI3K), in 3T3-L1 adipocytes. Moreover, treatment with the PI3K inhibitor LY294002 completely blocked EPA-stimulatory action on apelin mRNA gene expression (p<0.001), but not modified the stimulatory effect of EPA on basal apelin secretion. Furthermore, the stimulatory effect of EPA on basal apelin release was also observed in the presence of Actinomycin D and Cycloheximide, suggesting that EPA might also regulate apelin secretion by via post-transcriptional mechanisms. These findings suggest that the mechanisms mediating EPA-induced apelin synthesis and/or secretion are complex, involving steps that are PI3K dependent and steps that are PI3K independent.
Autores: Marrades, María Pilar; González-Muniesa, P; Martínez, JA; et al.
Revista: OBESITY FACTS
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: Moreno-Aliaga MJ;
Título: Tejido adiposo
Revista: AULA DE LA FARMACIA
ISSN 1697-543X  Vol. 6  Nº 67  2010  págs. 6 - 20
Autores: García, Diego Fernando; Arellano, A.V.; Campión, Francisco Javier; et al.
Revista: Obesity Reviews
ISSN 1467-7881  Vol. 11  2010  págs. 126
Autores: Vasconcelos, A. G.; Lorente, Silvia; Bressan, J.; et al.
Revista: NUTRICION HOSPITALARIA
ISSN 0212-1611  Vol. 25  Nº Supl. 1  2010  págs. 187
Autores: Fernández, Marta; et al.
Libro:  Obesity: Oxidative Stress and Dietary Antioxidants
2018  págs. 63 - 92
Autores: Zulet, María de los Ángeles; Moreno-Aliaga MJ; Martínez, JA;
Libro:  Adipose tissue biology
2017  págs. 319 - 382
Body weight and fat content as well as enery metabolism depends on several factors such as food intake, nutrient-associated turnover, thermogenesis, and physical activity. These elements underlie complex interrelated feedback mechanisms, which are affected by personal genetic traits. A number of investigations have evidenced that not all calorie may count equal and that some specific biofactors occurring in foods may affect energy efficiency and fat deposition. Thus, the role of protein and specific amino acids, the glycemic load of different carbohydrates and foods, the type of fats, as well as the involvement of some food components with bioactive functions affecting the energy equation are being ascertained, since they can influence body composition and adiposity. Indeed, moderately high protein intake, carbohydrate with low glycemic index, n-3 fatty acids, calcium, and some thermogenic substances and antioxidants have been found to possibly contribute to reduce the body fat content. Many of these findings have been supported not only through epidemiological studies, but also by animal and cell investigations as well as through controlled nutritional interventions in humans. A better understanding of the putative involved mechanisms concerning the effects of individual fatty acids such as conjugated linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid in body composition maintenance, as well as the identification of new bioactive compounds affecting lipid turnover and energy metabolism will open the way for a better control and management of fat deposition in different stages of the life cycle, since some of them are able to control relevant metabolic pathways at the molecular level, which will contribute to precision nutrition.
Autores: Zulet, María de los Ángeles; Moreno-Aliaga MJ; Martínez, JA;
Libro:  Adipose Tissue Biology
2012  págs. 271 - 315
Summary: In conjunction with the obesity zepidemicy in the developed world there has been an exponential increase in academic and medical interest in adipose tissue
Autores: Zulet, María de los Ángeles; Moreno-Aliaga MJ; Martínez, JA;
Libro:  Adipose tissue biology
2012  págs. 271 - 315
The stability of body weight and fat composition depends on several components such as food intake, nutrient-associated turnover, thermogenesis, and physical activity. These elements underlie complex interrelated feedback mechanisms, which are affected by personal genetic traits. A number of investigations have evidence that not all calories count equal and that some specifi c biofactors occurring in foods may affect energy effi ciency and fat deposition. Thus, the role of protein and specifi c amino acids, the glycemic load of different carbohydrates and foods, the type of fat, as well as the involvement of some food components with bioactive functions affecting the energy equation are being ascertained, since they can infl uence body composition and adiposity. Indeed, moderately high protein intake, carbohydrate with low glycemic index, n -3 fatty acids, calcium, and some thermogenic substances and antioxidants have been found to possibly contribute to reduce the body fat content. Many of these fi ndings have been supported not only through epidemiological studies, but also by animal and cell investigations as well as through controlled nutritional interventions in humans. A better understanding of the putative involved mechanisms in the effects of individual fatty acids such as conjugated linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid in body composition maintenance, as well as the identifi cation of new bioactive compounds affecting lipid turnover and energy metabolism will open the way for a better control and management of fat deposition in different stages of the life cycle, since some of them are able to control relevant metabolic pathways at the molecular level.
Autores: Fernández, Marta; Lorente, Silvia; Moreno-Aliaga MJ;
Libro:  Fundamentos de nutrición y dietética : bases metodológicas y aplicaciones.
2011  págs. 351 - 354
Autores: Lorente, Silvia; Moreno-Aliaga MJ;
Libro:  Fundamentos de nutrición y dietética : bases metodológicas y aplicaciones
2011  págs. 275 - 279
Autores: Lorente, Silvia; Moreno-Aliaga MJ;
Libro:  Fundamentos de nutrición y dietética : bases metodológicas y aplicaciones
2011  págs. 145 - 150
Autores: Moreno-Aliaga MJ; Lorente, Silvia; Martínez, JA;
Libro:  Inmunonutrición en la salud y en la enfermedad
2011  págs. 322 - 335
Autores: Moreno-Aliaga MJ;
Libro:  Fundamentos de nutrición y dietética : bases metodológicas y aplicaciones
2011  págs. 123 - 126

ACTIVIDAD DOCENTE