ABSTRACT
Chemerin is a pro-inflammatory adipokine that is increased in obesity and associated with obesity-related comorbidities. The aim of this study was to investigate the effects of omega-3 polyunsaturated fatty acids, eicosapentaenoic and docosahexaenoic acids (EPA and DHA), on basal and tumor necrosis factor-α (TNF-α)-induced chemerin production in 3T3-L1 and human subcutaneous cultured adipocytes. The potential involvement of G protein-coupled receptor 120 (GPR120), as well as the actions of DHA-derived specialized proresolving lipid mediators (SPMs), resolvin D1 and D2 (RvD1 and RvD2) and maresin 1 (MaR1), were also evaluated. DHA significantly lowered both basal and TNF-α-stimulated chemerin production in 3T3-L1 and human adipocytes. EPA did not modify basal chemerin production, while it attenuated the induction of chemerin by TNF-α. Silencing of GPR120 using siRNA blocked the ability of DHA and EPA to reduce TNF-α-induced chemerin secretion. Interestingly, treatment with the DHA-derived SPMs RvD1, RvD2 and MaR1 also reversed the stimulatory effect of TNF-α on chemerin production in human adipocytes.
Subject(s)
Adipocytes/drug effects , Chemokines/metabolism , Fatty Acids, Omega-3/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Receptors, G-Protein-Coupled/metabolism , 3T3-L1 Cells , Adipocytes/metabolism , Animals , Cells, Cultured , Chemokines/genetics , Intercellular Signaling Peptides and Proteins/genetics , Mice , Receptors, G-Protein-Coupled/genetics , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
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 µM) 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-1α) 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-α 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.
Subject(s)
Adipocytes, Beige/metabolism , Adipocytes, White/metabolism , Eicosapentaenoic Acid/metabolism , Gene Expression Regulation, Enzymologic , Mitochondrial Dynamics , Organelle Biogenesis , Subcutaneous Fat, Abdominal/metabolism , Acyl-CoA Oxidase/chemistry , Acyl-CoA Oxidase/genetics , Acyl-CoA Oxidase/metabolism , Adipocytes, Beige/enzymology , Adipocytes, Beige/pathology , Adipocytes, White/enzymology , Adipocytes, White/pathology , Adipogenesis , Biomarkers/metabolism , Body Mass Index , Carnitine O-Palmitoyltransferase/chemistry , Carnitine O-Palmitoyltransferase/genetics , Carnitine O-Palmitoyltransferase/metabolism , Cells, Cultured , Diacylglycerol O-Acyltransferase/antagonists & inhibitors , Diacylglycerol O-Acyltransferase/genetics , Diacylglycerol O-Acyltransferase/metabolism , Energy Metabolism , Fatty Acid Synthases/antagonists & inhibitors , Fatty Acid Synthases/genetics , Fatty Acid Synthases/metabolism , Female , Humans , Lipid Metabolism , Osmolar Concentration , Stearoyl-CoA Desaturase/antagonists & inhibitors , Stearoyl-CoA Desaturase/genetics , Stearoyl-CoA Desaturase/metabolism , Subcutaneous Fat, Abdominal/enzymology , Subcutaneous Fat, Abdominal/pathologyABSTRACT
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 (100200 μM) or alpha-lipoic acid (100250 μM) 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 μM) 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 endpoint of the study. The data from the OGTT suggest that glucose is not a direct contributing factor of irisin release. The higher irisin levels observed in overweight/obese conditions could be a protective response of organism to early glucose impairments
Subject(s)
Female , Humans , Glucose Metabolism Disorders/physiopathology , Obesity/physiopathology , Overweight/physiopathology , Eicosapentaenoic Acid/pharmacokinetics , Thioctic Acid/pharmacokinetics , Myosins/pharmacokinetics , Adipokines/pharmacokineticsABSTRACT
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 α-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), α-lipoic acid (0.3 g/day) or both EPA + α-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 µM) or α-lipoic acid (100-250 µM) 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 α-lipoic acid (250 µM) 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 α-lipoic acid supplementation. Moreover, plasma irisin levels were positively associated with higher glucose concentrations at beginning and at endpoint of the study. The data from the OGTT suggest that glucose is not a direct contributing factor of irisin release. The higher irisin levels observed in overweight/obese conditions could be a protective response of organism to early glucose impairments.
Subject(s)
Eicosapentaenoic Acid/administration & dosage , Fibronectins/blood , Glucose/metabolism , Obesity/blood , Thioctic Acid/administration & dosage , Adipocytes, White/drug effects , Adipocytes, White/metabolism , Adult , Blood Glucose , Caloric Restriction , Cells, Cultured , Double-Blind Method , Female , Humans , Middle Aged , Obesity/diet therapy , Subcutaneous Fat/pathology , Treatment Outcome , Weight Loss , Young AdultABSTRACT
Several studies have suggested that oxidative stress might cause and aggravate the inflammatory state associated with obesity and could be the link between excessive weight gain and its related disorders such as insulin resistance and cardiovascular diseases. Thus, antioxidant treatment has been proposed as a therapy to prevent and manage obesity and associated complications. Therefore, the aim of the present study was to investigate the effects of supplementation of a standard or high fat diet with the antioxidant lipoic acid (LA) during 56 days, on body weight gain, adiposity, feed efficiency and intestinal sugar absorption, in male Wistar rats. LA supplementation induced a lower body weight gain and adipose tissue size in both control or high fat fed rats accompanied by a reduction in food intake. The group fed on a high fat diet and treated with LA (OLIP group) showed a lower body weight gain than its corresponding Pair-Fed (PF) group (P < 0.05), which received the same amount of food than LA-treated animals but with no LA. In fact, LA induced a reduction on feed efficiency and also significantly decreased intestinal alpha-methylglucoside (alpha-MG) absorption both in lean and obese rats. These results suggest that the beneficial effects of dietary supplementation with LA on body weight gain are mediated, at least in part, by the reduction observed in food intake and feed efficiency. Furthemore, the inhibitory action of LA on intestinal sugar transport could explain in part the lower feed efficiency observed in LA-treated animals and therefore, highlighting the beneficial effects of LA on obesity.
Subject(s)
Carbohydrate Metabolism/drug effects , Dietary Fats/pharmacology , Intestinal Absorption/drug effects , Thioctic Acid/pharmacology , Weight Gain/drug effects , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Animals , Eating , Male , Organ Size , Rats , Rats, WistarABSTRACT
Several studies have suggested that oxidative stress might cause and aggravate theinflammatory state associated with obesity and could be the link between excessiveweight gain and its related disorders such as insulin resistance and cardiovascular diseases.Thus, antioxidant treatment has been proposed as a therapy to prevent andmanage obesity and associated complications. Therefore, the aim of the present studywas to investigate the effects of supplementation of a standard or high fat diet withthe antioxidant lipoic acid (LA) during 56 days, on body weight gain, adiposity, feedefficiency and intestinal sugar absorption, in male Wistar rats. LA supplementationinduced a lower body weight gain and adipose tissue size in both control or high fatfed rats accompanied by a reduction in food intake. The group fed on a high fat dietand treated with LA (OLIP group) showed a lower body weight gain than its correspondingPair-Fed (PF) group (P<0.05), which received the same amount of foodthan LA-treated animals but with no LA. In fact, LA induced a reduction on feedefficiency and also significantly decreased intestinal α-methylglucoside (α-MG)absorption both in lean and obese rats. These results suggest that the beneficial effectsof dietary supplementation with LA on body weight gain are mediated, at least inpart, by the reduction observed in food intake and feed efficiency. Furthemore, theinhibitory action of LA on intestinal sugar transport could explain in part the lowerfeed efficiency observed in LA-treated animals and therefore, highlighting the beneficialeffects of LA on obesity(AU)
Varios estudios han sugerido que el estresoxidativo podria actuar como desencadenantey agravante del estado inflamatorio asociado ala obesidad y podria ser un potencial nexo deunion entre la excesiva ganancia de peso y lasco-morbilidades asociadas. Asi, se ha propuestoel tratamiento con antioxidantes naturalescomo posible terapia contra el desarrollo deobesidad asi como sus complicaciones asociadas.Por ello, el objeto del presente trabajo fueinvestigar en ratas Wistar macho los efectos dela suplementacion de una dieta estandar o altaen grasa con un antioxidante, el acido lipoico(AL) (0,25g/ 100g de comida) durante 56 diassobre la ganancia de peso corporal, la adiposidad,la eficiencia metabolica y la absorcionintestinal de azucares. La suplementacion de ladieta con AL indujo una menor ganancia depeso corporal y redujo el tamano del tejidoadiposo blanco total, tanto en ratas alimentadascon dieta control como alta en grasa. Ademas,disminuyo la ingesta. La ganancia de pesoen el grupo alimentado con dieta alta en grasay AL fue menor que la de su correspondientegrupo Pair-Fed (P<0,05), el cual recibia lamisma cantidad de comida que los animalestratados con AL pero sin este acido. De hecho,la suplementacion con acido lipoico redujo laeficiencia metabolica y disminuyo significativamentela absorcion intestinal de ƒ¿-metilglucosido(ƒ¿-MG) tanto en ratas control comoobesas. Estos resultados sugieren que los efectosbeneficiosos de la suplementacion de ladieta con AL sobre la ganancia de peso corporalestan mediados, al menos en parte, por lareduccion observada en la ingesta de comida yen la eficiencia metabolica. Ademas, la accioninhibitoria del AL sobre el transporte intestinalde azucares podria explicar, en parte, la menoreficiencia metabolica observada en los animalestratados con AL justificando, por consiguiente,los efectos beneficiosos del AL sobre la obesidad(AU)
