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© Research
Publication : Cell metabolism

Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity

Team: Archived: Cytokine Signaling
Member: Sandra Pellegrini
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell metabolism - 01 Dec 2012

Derecka M, Gornicka A, Koralov SB, Szczepanek K, Morgan M, Raje V, Sisler J, Zhang Q, Otero D, Cichy J, Rajewsky K, Shimoda K, Poli V, Strobl B, Pellegrini S, Harris TE, Seale P, Russell AP, McAinch AJ, O'Brien PE, Keller SR, Croniger CM, Kordula T, Larner AC

Link to Pubmed [PMID] – 23217260

Cell Metab. 2012 Dec;16(6):814-24

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.