Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity.
Cell Metab
; 16(6): 814-24, 2012 Dec 05.
Article
in En
| MEDLINE
| ID: mdl-23217260
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adipose Tissue, Brown
/
STAT3 Transcription Factor
/
TYK2 Kinase
/
Obesity
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Metab
Year:
2012
Document type:
Article