title: Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) α1.
abstract: 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) α1 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-γ coactivator 1α, 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 AMPKα1 phosphorylation and differentiated SVC oxygen consumption. Such changes were absent in cells lacking AMPKα1, showing that AMPKα1 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 AMPKα1 activation and suggest that its beneficial antiobesity effects may be partly due to the browning of WAT and, as a consequence, increased oxygen consumption.
authors.affiliation: 1] College of Animal Science, ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, China [2] Department of Animal Sciences, Washington Center for Muscle Biology, Washington State University, Pullman, WA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Animal Sciences, Washington Center for Muscle Biology, Washington State University, Pullman, WA, USA.
authors.forename: X
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Animal Sciences, Washington Center for Muscle Biology, Washington State University, Pullman, WA, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Animal Sciences, Washington Center for Muscle Biology, Washington State University, Pullman, WA, USA.
authors.forename: X
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Animal Sciences, Washington Center for Muscle Biology, Washington State University, Pullman, WA, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Rogers
authors.affiliation: School of Food Sciences, Washington State University, Pullman, WA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Animal Sciences, Washington Center for Muscle Biology, Washington State University, Pullman, WA, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Rodgers
authors.affiliation: College of Animal Science, ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Animal Sciences, Washington Center for Muscle Biology, Washington State University, Pullman, WA, USA.
authors.forename: M V
authors.initials: MV
authors.lastname: Dodson
authors.affiliation: Department of Animal Sciences, Washington Center for Muscle Biology, Washington State University, Pullman, WA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Du
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D052437:Adipocytes, Brown / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D059305:Diet, High-Fat; D004435:Eating; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007473:Ion Channels / Q000378:metabolism*; D051379:Mice; D024101:Mitochondrial Proteins / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D000071256:Uncoupling Protein 1
chemical_list: D000975:Antioxidants; D007473:Ion Channels; D024101:Mitochondrial Proteins; D013267:Stilbenes; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D000242:Cyclic AMP; C548179:Prkaa1 protein, mouse; D055372:AMP-Activated Protein Kinases; D000077185:Resveratrol