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Cell Metab. 2011 Jul 6;14(1):67-79. doi: 10.1016/j.cmet.2011.04.013.

Protection from obesity and diabetes by blockade of TGF-β/Smad3 signaling.

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  • 1Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Clinical Research Center, South Drive and Old Georgetown Road, Bethesda, MD 20892, USA.

Abstract

Imbalances in glucose and energy homeostasis are at the core of the worldwide epidemic of obesity and diabetes. Here, we illustrate an important role of the TGF-β/Smad3 signaling pathway in regulating glucose and energy homeostasis. Smad3-deficient mice are protected from diet-induced obesity and diabetes. Interestingly, the metabolic protection is accompanied by Smad3(-)(/-) white adipose tissue acquiring the bioenergetic and gene expression profile of brown fat/skeletal muscle. Smad3(-/-) adipocytes demonstrate a marked increase in mitochondrial biogenesis, with a corresponding increase in basal respiration, and Smad3 acts as a repressor of PGC-1α expression. We observe significant correlation between TGF-β1 levels and adiposity in rodents and humans. Further, systemic blockade of TGF-β signaling protects mice from obesity, diabetes, and hepatic steatosis. Together, these results demonstrate that TGF-β signaling regulates glucose tolerance and energy homeostasis and suggest that modulation of TGF-β activity might be an effective treatment strategy for obesity and diabetes.

Copyright © 2011 Elsevier Inc. All rights reserved.

Comment in

PMID:
21723505
[PubMed - indexed for MEDLINE]
PMCID:
PMC3169298
Free PMC Article

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