title: Resveratrol inhibits lipogenesis of 3T3-L1 and SGBS cells by inhibition of insulin signaling and mitochondrial mass increase.
abstract: Resveratrol is attracting much interest because of its potential to decrease body weight and increase life span, influencing liver and muscle function by increasing mitochondrial mass and energy expenditure. Even though resveratrol was already shown to reduce the adipose tissue mass in animal models, its effects on mitochondrial mass and network structure in adipocytes have not yet been studied. For this purpose, we investigated the effect of resveratrol on mitochondrial mass increase and remodeling during adipogenic differentiation of two in vitro models of adipocyte biology, the murine 3T3-L1 cell line and the human SGBS cell strain. We confirm that resveratrol inhibits lipogenesis in differentiating adipocytes, both mouse and human. We further show that this is linked to inhibition of the normally observed mitochondrial mass increase and mitochondrial remodeling. At the molecular level, the anti-lipogenic effect of resveratrol seems to be mediated by a blunted expression increase and an inhibition of acetyl-CoA carboxylase (ACC). This is one of the consequences of an inhibited insulin-induced signaling via Akt, and maintained signaling via AMP-activated protein kinase. The anti-lipogenic effect of resveratrol is further modulated by expression levels of mitochondrial ATAD3, consistent with the emerging role of this protein as an important regulator of mitochondrial biogenesis and lipogenesis. Our data suggest that resveratrol acts on differentiating preadipocytes by inhibiting insulin signaling, mitochondrial biogenesis, and lipogenesis, and that resveratrol-induced reduction of mitochondrial biogenesis and lipid storage contribute to adipose tissue weight loss in animals and humans.
authors.affiliation: Univ. Grenoble Alpes, Laboratory for Fundamental and Applied Bioenergetics (LBFA), Grenoble, France; Inserm U1055, Grenoble, France.
authors.forename: Shuijie
authors.initials: S
authors.lastname: Li
authors.affiliation: Univ. Grenoble Alpes, Laboratory for Fundamental and Applied Bioenergetics (LBFA), Grenoble, France; Inserm U1055, Grenoble, France.
authors.forename: Célia
authors.initials: C
authors.lastname: Bouzar
authors.affiliation: Univ. Grenoble Alpes, Laboratory for Fundamental and Applied Bioenergetics (LBFA), Grenoble, France; Inserm U1055, Grenoble, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Cottet-Rousselle
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Obesity Unit Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Germany.
authors.forename: Ivana
authors.initials: I
authors.lastname: Zagotta
authors.affiliation: Univ. Grenoble Alpes, Laboratory for Fundamental and Applied Bioenergetics (LBFA), Grenoble, France; Inserm U1055, Grenoble, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lamarche
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Obesity Unit Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
authors.affiliation: Univ. Grenoble Alpes, Laboratory for Fundamental and Applied Bioenergetics (LBFA), Grenoble, France; Inserm U1055, Grenoble, France.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Tokarska-Schlattner
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Obesity Unit Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Germany.
authors.forename: Pamela
authors.initials: P
authors.lastname: Fischer-Posovszky
authors.affiliation: Univ. Grenoble Alpes, Laboratory for Fundamental and Applied Bioenergetics (LBFA), Grenoble, France; Inserm U1055, Grenoble, France.
authors.forename: Uwe
authors.initials: U
authors.lastname: Schlattner
authors.affiliation: Univ. Grenoble Alpes, Laboratory for Fundamental and Applied Bioenergetics (LBFA), Grenoble, France; Inserm U1055, Grenoble, France. Electronic address: Denis.Rousseau@univ-grenoble-alpes.fr.
authors.forename: Denis
authors.initials: D
authors.lastname: Rousseau
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000074183:ATPases Associated with Diverse Cellular Activities; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050155:Lipogenesis / Q000187:drug effects*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; C582415:Atad3a protein, mouse; D007328:Insulin; D024101:Mitochondrial Proteins; D013267:Stilbenes; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; D000103:Acetyl-CoA Carboxylase; D000077185:Resveratrol
keywords: 3T3-L1; AMPK; ATAD3; Adipocyte; Akt; Mitochondria; Resveratrol; SGBS