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

Hariom Yadav, Celia Quijano, Anil K. Kamaraju, Oksana Gavrilova, Rana Malek, Weiping Chen, Patricia Zerfas, Duan Zhigang, Elizabeth C. Wright, Christina Stuelten, Peter Sun, Scott Lonning, Monica Skarulis, Anne E. Sumner, Toren Finkel, Sushil G. Rane

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)67-79
Number of pages13
JournalCell Metabolism
Volume14
Issue number1
DOIs
StatePublished - Jul 6 2011
Externally publishedYes

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Obesity
Homeostasis
Glucose
White Adipose Tissue
Brown Adipose Tissue
Adiposity
Organelle Biogenesis
Transcriptome
Adipocytes
Energy Metabolism
Rodentia
Respiration
Skeletal Muscle
Diet
Liver

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Yadav, H., Quijano, C., Kamaraju, A. K., Gavrilova, O., Malek, R., Chen, W., ... Rane, S. G. (2011). Protection from obesity and diabetes by blockade of TGF-β/Smad3 signaling. Cell Metabolism, 14(1), 67-79. https://doi.org/10.1016/j.cmet.2011.04.013

Protection from obesity and diabetes by blockade of TGF-β/Smad3 signaling. / Yadav, Hariom; Quijano, Celia; Kamaraju, Anil K.; Gavrilova, Oksana; Malek, Rana; Chen, Weiping; Zerfas, Patricia; Zhigang, Duan; Wright, Elizabeth C.; Stuelten, Christina; Sun, Peter; Lonning, Scott; Skarulis, Monica; Sumner, Anne E.; Finkel, Toren; Rane, Sushil G.

In: Cell Metabolism, Vol. 14, No. 1, 06.07.2011, p. 67-79.

Research output: Contribution to journalArticle

Yadav, H, Quijano, C, Kamaraju, AK, Gavrilova, O, Malek, R, Chen, W, Zerfas, P, Zhigang, D, Wright, EC, Stuelten, C, Sun, P, Lonning, S, Skarulis, M, Sumner, AE, Finkel, T & Rane, SG 2011, 'Protection from obesity and diabetes by blockade of TGF-β/Smad3 signaling', Cell Metabolism, vol. 14, no. 1, pp. 67-79. https://doi.org/10.1016/j.cmet.2011.04.013
Yadav H, Quijano C, Kamaraju AK, Gavrilova O, Malek R, Chen W et al. Protection from obesity and diabetes by blockade of TGF-β/Smad3 signaling. Cell Metabolism. 2011 Jul 6;14(1):67-79. https://doi.org/10.1016/j.cmet.2011.04.013
Yadav, Hariom ; Quijano, Celia ; Kamaraju, Anil K. ; Gavrilova, Oksana ; Malek, Rana ; Chen, Weiping ; Zerfas, Patricia ; Zhigang, Duan ; Wright, Elizabeth C. ; Stuelten, Christina ; Sun, Peter ; Lonning, Scott ; Skarulis, Monica ; Sumner, Anne E. ; Finkel, Toren ; Rane, Sushil G. / Protection from obesity and diabetes by blockade of TGF-β/Smad3 signaling. In: Cell Metabolism. 2011 ; Vol. 14, No. 1. pp. 67-79.
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