Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) [alpha]1

• Published in: International Journal of Obesity 2015-06, Vol.39 (6), p.967
• Main Authors: Zhu, M, Yang, Q, Wang, S, Liang, X, Fu, X, Rogers, C J, Du, M, Rodgers, B D
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipose tissue; Adipose tissues; Animal models; Animal sciences; Body fat; Diet; Drug therapy; Energy; Fat cells; Fatty acids; Food; Health aspects; Kinases; Metabolism; Mitochondrial DNA; Nutrition research; Obesity; Oxygen consumption; Physiological aspects; Protein kinases; Proteins; Resveratrol
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2015.23

Objective: Development of brown-like/beige adipocytes in white adipose tissue (WAT) helps to reduce obesity. Thus we investigated the effects of resveratrol, a dietary polyphenol capable of preventing obesity and related complications in humans and animal models, on brown-like adipocyte formation in inguinal WAT (iWAT). Methods: CD1 female mice (5-month old) were fed a high-fat diet with/without 0.1% resveratrol. In addition, primary stromal vascular cells separated from iWAT were subjected to resveratrol treatment. Markers of brown-like (beige) adipogenesis were measured and the involvement of AMP-activated protein kinase (AMPK) [alpha]1 was assessed using conditional knockout. Results: Resveratrol significantly increased mRNA and/or protein expression of brown adipocyte markers, including uncoupling protein 1 (UCP1), PR domain-containing 16, cell death-inducing DFFA-like effector A, elongation of very long-chain fatty acids protein 3, peroxisome proliferator-activated receptor-[gamma] coactivator 1[alpha], cytochrome c and pyruvate dehydrogenase, in differentiated iWAT stromal vascular cells (SVCs), suggesting that resveratrol induced brown-like adipocyte formation in vitro. Concomitantly, resveratrol markedly enhanced AMPK[alpha]1 phosphorylation and differentiated SVC oxygen consumption. Such changes were absent in cells lacking AMPK[alpha]1, showing that AMPK[alpha]1 is a critical mediator of resveratrol action. Resveratrol also induced beige adipogenesis in vivo along with the appearance of multiocular adipocytes, increased UCP1 expression and enhanced fatty acid oxidation. Conclusions: Resveratrol induces brown-like adipocyte formation in iWAT via AMPK[alpha]1 activation and suggest that its beneficial antiobesity effects may be partly due to the browning of WAT and, as a consequence, increased oxygen consumption.