title: α-Lipoic acid treatment increases mitochondrial biogenesis and promotes beige adipose features in subcutaneous adipocytes from overweight/obese subjects.
abstract: α-Lipoic acid (α-Lip) is a natural occurring antioxidant with beneficial anti-obesity properties. The aim of this study was to investigate the putative effects of α-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 α-Lip (100 and 250μM) for 24h 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-1α) pathway was also evaluated. Our results showed that α-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-1α 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 α-Lip-treated adipocytes exhibited some morphological characteristics of brown mitochondria, and α-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, α-Lip up-regulated PR domain containing 16 (Prdm16) mRNA levels in treated adipocytes. Therefore, our study suggests the ability of α-Lip to promote mitochondrial biogenesis and brown-like remodeling in cultured white subcutaneous adipocytes from overweight/obese donors.
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Fernández-Galilea
authors.affiliation: HIV and Associated Metabolic Alterations Unit, Infectious Diseases Department, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Pérez-Matute
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain; Faculty of Health and Physical Activity Science, University SEK, Santiago, Chile.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Prieto-Hontoria
authors.affiliation: INSERM, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Houssier
authors.affiliation: Department of Histology and Pathology, University of Navarra, Pamplona, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Burrell
authors.affiliation: INSERM, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France; Toulouse University Hospitals, Laboratory of Clinical Biochemistry, Toulouse, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain; Center for Nutrition Research, University of Navarra, Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martínez
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain; Center for Nutrition Research, University of Navarra, Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: mjmoreno@unav.es.
authors.forename: María J
authors.initials: MJ
authors.lastname: Moreno-Aliaga
mesh_terms: D000107:Acetylation / Q000187:drug effects; D052437:Adipocytes, Brown / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000975:Antioxidants / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D056915:DNA Copy Number Variations / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000819:agonists / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D063269:Mitochondrial Turnover / Q000187:drug effects*; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D061251:Primary Cell Culture; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D050151:Subcutaneous Fat / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; C502539:CIDEA protein, human; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; C495633:NRF1 protein, human; D051266:Nuclear Respiratory Factor 1; C486497:PPARGC1A protein, human; C416371:PRDM16 protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020825:T-Box Domain Proteins; C108625:TBX1 protein, human; C499631:TFAM protein, human; D014157:Transcription Factors; D008063:Thioctic Acid; D010088:Oxidoreductases; C576470:ACOX2 protein, human; C577474:CPT1A protein, human; D002334:Carnitine O-Palmitoyltransferase; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Brown adipose tissue; Human adipocyte; Mitochondrial biogenesis; Obesity; α-Lipoic acid