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Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity

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journal contribution
posted on 05.12.2012, 00:00 authored by M Derecka, A Gornicka, S Koralov, K Szczepanek, M Morgan, V Raje, J Sisler, Q Zhang, D Otero, J Cichy, K Rajewsky, K Shimoda, V Poli, B Strobl, S Pellegrini, T Harris, P Seale, Aaron RussellAaron Russell, A McAinch, P O'Brien, S Keller, C Croniger, T Kordula, A Larner
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.

History

Journal

Cell metabolism

Volume

16

Issue

6

Pagination

814 - 824

Publisher

Cell Press

Location

Cambridge, Mass.

ISSN

1550-4131

eISSN

1932-7420

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2012, Elsevier