| First Author | Yadav H | Year | 2011 |
| Journal | Cell Metab | Volume | 14 |
| Issue | 1 | Pages | 67-79 |
| PubMed ID | 21723505 | Mgi Jnum | J:176081 |
| Mgi Id | MGI:5288290 | Doi | 10.1016/j.cmet.2011.04.013 |
| Citation | Yadav H, et al. (2011) Protection from obesity and diabetes by blockade of TGF-beta/Smad3 signaling. Cell Metab 14(1):67-79 |
| abstractText | 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-beta/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-1alpha expression. We observe significant correlation between TGF-beta1 levels and adiposity in rodents and humans. Further, systemic blockade of TGF-beta signaling protects mice from obesity, diabetes, and hepatic steatosis. Together, these results demonstrate that TGF-beta signaling regulates glucose tolerance and energy homeostasis and suggest that modulation of TGF-beta activity might be an effective treatment strategy for obesity and diabetes. |
