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Tyk2 and stat3 regulate brown adipose tissue differentiation and obesity

Derecka, Marta and Gornicka, Agnieszka and Koralov, Sergei B and Szczepanek, Karol and Morgan, Magdalena and Raje, Vidish and Sisler, Jennifer and Zhang, Qifang and Otero, Dennis and Cichy, Joanna and Rajewsky, Klaus and Shimoda, Kazuy and Poli, Valeria and Strobl, Birgit and Pellegrini, Sandra and Harris, Thurl E and Seale, Patrick and Russell, Aaron P and McAinch, Andrew and O’Brien, Paul E and Keller, Susanna R and Croniger, Colleen M and Kordula, Tomasz and Larner, Andrew C (2012) Tyk2 and stat3 regulate brown adipose tissue differentiation and obesity. Cell Metabolism, 16 (6). pp. 814-824. ISSN 1550-4131

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Abstract

Mice lacking the Jak tyrosine kinase member Tyk2 become progressively obese due to aberrant development of Myf5+ brown adipose tissue (BAT). Tyk2 RNA levels in BAT and skeletal muscle, which shares a common progenitor with BAT, are dramatically decreased in mice placed on a high-fat diet and in obese humans. Expression of Tyk2 or the constitutively active form of the transcription factor Stat3 (CAStat3) restores differentiation in Tyk2−/− brown preadipocytes. Furthermore, Tyk2−/− mice expressing CAStat3 transgene in BAT also show improved BAT development, normal levels of insulin, and significantly lower body weights. Stat3 binds to PRDM16, a master regulator of BAT differentiation, and enhances the stability of PRDM16 protein. These results define Tyk2 and Stat3 as critical determinants of brown fat lineage and suggest that altered levels of Tyk2 are associated with obesity in both rodents and humans.

Item Type: Article
Uncontrolled Keywords: ResPubID25599, insulin, Prdm16 protein, protein kinase TYK2, regulator protein, RNA, STAT3 protein, unclassified drug
Subjects: Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
FOR Classification > 0601 Biochemistry and Cell Biology
Depositing User: Yimin Zeng
Date Deposited: 14 Jun 2013 02:33
Last Modified: 08 Aug 2013 05:51
URI: http://vuir.vu.edu.au/id/eprint/21517
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Citations in Scopus: 2 - View on Scopus

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