Document Detail


Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity.
MedLine Citation:
PMID:  23217260     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Marta Derecka; Agnieszka Gornicka; Sergei B Koralov; Karol Szczepanek; Magdalena Morgan; Vidisha Raje; Jennifer Sisler; Qifang Zhang; Dennis Otero; Joanna Cichy; Klaus Rajewsky; Kazuya Shimoda; Valeria Poli; Birgit Strobl; Sandra Pellegrini; Thurl E Harris; Patrick Seale; Aaron P Russell; Andrew J McAinch; Paul E O'Brien; Susanna R Keller; Colleen M Croniger; Tomasz Kordula; Andrew C Larner
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell metabolism     Volume:  16     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-10     Completed Date:  2013-05-22     Revised Date:  2013-12-11    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  814-24     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue, Brown / cytology,  growth & development,  metabolism*
Animals
Cell Differentiation
Cells, Cultured
DNA-Binding Proteins / metabolism
Humans
Insulin
Mice
Mice, Knockout
Obesity / metabolism*,  pathology
Protein Binding
STAT3 Transcription Factor / genetics,  metabolism*
TYK2 Kinase / deficiency,  genetics,  metabolism*
Transcription Factors / metabolism
Weight Loss
Grant Support
ID/Acronym/Agency:
R01 AI059710/AI/NIAID NIH HHS; R01 AI059710-01/AI/NIAID NIH HHS; R01 GM101677/GM/NIGMS NIH HHS; R21 AI088487/AI/NIAID NIH HHS; R21 AI088487/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Insulin; 0/Prdm16 protein, mouse; 0/STAT3 Transcription Factor; 0/Transcription Factors; EC 2.7.10.2/TYK2 Kinase
Comments/Corrections

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