russell-tyk2and-2012.pdf (1.23 MB)
Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity
journal contribution
posted on 2012-12-05, 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 LarnerMice 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 metabolismVolume
16Issue
6Pagination
814 - 824Publisher
Cell PressLocation
Cambridge, Mass.Publisher DOI
Link to full text
ISSN
1550-4131eISSN
1932-7420Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2012, ElsevierUsage metrics
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