Protection from Obesity and Diabetes by Blockade of TGF-β/Smad3 Signaling

被引：575

作者：

Yadav, Hariom ^{[1
]}

Quijano, Celia ^{[2
,10
]}

Kamaraju, Anil K. ^{[1
]}

Gavrilova, Oksana ^{[3
]}

Malek, Rana ^{[1
]}

Chen, Weiping ^{[4
]}

Zerfas, Patricia ^{[5
]}

Duan Zhigang ^{[6
]}

Wright, Elizabeth C. ^{[6
]}

Stuelten, Christina ^{[7
]}

Sun, Peter ^{[8
]}

Lonning, Scott ^{[9
]}

Skarulis, Monica ^{[1
]}

Sumner, Anne E. ^{[1
]}

Finkel, Toren ^{[2
]}

Rane, Sushil G. ^{[1
]}

机构：

[1] NIDDK, Diabet Endocrinol & Obes Branch, Bethesda, MD 20892 USA

[2] NHLBI, Ctr Mol Med, Bethesda, MD 20892 USA

[3] Mouse Metab Core Lab, Bethesda, MD 20892 USA

[4] Genom Core Facil, Bethesda, MD 20892 USA

[5] Off Director, Off Res Serv, Bethesda, MD 20892 USA

[6] NIDDK, Off Res Serv, Bethesda, MD 20892 USA

[7] NCI, Bethesda, MD 20892 USA

[8] NIAID, NIH, Clin Res Ctr, Bethesda, MD 20892 USA

[9] Genzyme Corp, Framingham, MA 01701 USA

[10] Univ Republica, Dept Bioquim, Fac Med, Montevideo, Uruguay

来源：

CELL METABOLISM | 2011年 / 14卷 / 01期

关键词：

GROWTH-FACTOR-BETA; BROWN ADIPOSE-TISSUE; PLASMINOGEN-ACTIVATOR INHIBITOR-1; DIET-INDUCED OBESITY; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; ADIPOCYTE DIFFERENTIATION; TARGETED DISRUPTION; GENETIC-CONTROL; WHITE FAT;

D O I：

10.1016/j.cmet.2011.04.013

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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-1 alpha expression. We observe significant correlation between TGF-beta 1 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.

引用

页码：67 / 79

页数：13

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