title: Eicosapentaenoic acid promotes mitochondrial biogenesis and beige-like features in subcutaneous adipocytes from overweight subjects.
abstract: 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.
authors.affiliation: Department of Nutrition, Food Sciences and Physiology, School of Pharmacy, University of Navarra; Center for Nutrition Research, University of Navarra, Spain.
authors.forename: L M
authors.initials: LM
authors.lastname: Laiglesia
authors.affiliation: Department of Nutrition, Food Sciences and Physiology, School of Pharmacy, University of Navarra; Center for Nutrition Research, University of Navarra, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Lorente-Cebrián
authors.affiliation: Department of Nutrition, Food Sciences and Physiology, School of Pharmacy, University of Navarra.
authors.forename: P L
authors.initials: PL
authors.lastname: Prieto-Hontoria
authors.affiliation: Department of Nutrition, Food Sciences and Physiology, School of Pharmacy, University of Navarra.
authors.forename: M
authors.initials: M
authors.lastname: Fernández-Galilea
authors.affiliation: Department of Nutrition, Food Sciences and Physiology, School of Pharmacy, University of Navarra; Department of Nutrition and Health, University Federal of Viçosa, 36570-000, Viçosa, MG, Brazil.
authors.forename: S M R
authors.initials: SM
authors.lastname: Ribeiro
authors.affiliation: Department of Nutrition, Food Sciences and Physiology, School of Pharmacy, University of Navarra; Center for Nutrition Research, University of Navarra, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Sáinz
authors.affiliation: Department of Nutrition, Food Sciences and Physiology, School of Pharmacy, University of Navarra; Center for Nutrition Research, University of Navarra, Spain; CIBERobn, Physiopathology of Obesity and Nutrition, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Martínez
authors.affiliation: Department of Nutrition, Food Sciences and Physiology, School of Pharmacy, University of Navarra; Center for Nutrition Research, University of Navarra, Spain; CIBERobn, Physiopathology of Obesity and Nutrition, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. Electronic address: mjmoreno@unav.es.
authors.forename: M J
authors.initials: MJ
authors.lastname: Moreno-Aliaga
mesh_terms: D042962:Acyl-CoA Oxidase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000069797:Adipocytes, Beige / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D052438:Adipocytes, White / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D050156:Adipogenesis; D015415:Biomarkers / Q000378:metabolism; D015992:Body Mass Index; D002334:Carnitine O-Palmitoyltransferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000378:metabolism*; D004734:Energy Metabolism; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D050356:Lipid Metabolism; D063154:Mitochondrial Dynamics; D001678:Organelle Biogenesis; D009994:Osmolar Concentration; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D050507:Subcutaneous Fat, Abdominal / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers; D015118:Eicosapentaenoic Acid; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase; D042962:Acyl-CoA Oxidase; C494881:DGAT1 protein, human; C494885:DGAT2 protein, human; D051048:Diacylglycerol O-Acyltransferase; C577474:CPT1A protein, human; D002334:Carnitine O-Palmitoyltransferase; D064429:Fatty Acid Synthases
keywords: Browning; EPA; Fatty acid oxidation; Lipogenesis; Mitochondrial biogenesis; N-3 PUFAs