Journal
INTERNATIONAL JOURNAL OF OBESITY
Volume 39, Issue 6, Pages 967-976Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ijo.2015.23
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Funding
- National Institutes of Health [R01HD067449]
- National Natural Science Foundation of China [31372397]
- Muscular Dystrophy Association [216602]
- National Science Foundation [1147275]
- Agricultural Research Center at Washington State University, College of Agricultural, Human, and Natural Resource Sciences
- Division Of Integrative Organismal Systems
- Direct For Biological Sciences [1147275] Funding Source: National Science Foundation
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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 AMPKa1 activation and suggest that its beneficial antiobesity effects may be partly due to the browning of WAT and, as a consequence, increased oxygen consumption.
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