Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity

Derecka, Marta, Gornicka, Agnieszka, Koralov, Sergei B., Szczepanek, Karol, Morgan, Magdalena, Raje, Vicisha, Sisler, Jennifer, Zhang, Qifang, Otero, Dennis, Cichy, Joanna, Rajewsky, Klaus, Shimoda, Kazuya, Poli, Valeria, Strobl, Birgit, Pellegrini, Sandra, Harris, Thurl E., Seale, Patrick, Russell, Aaron P., McAinch, Andrew J., O'Brien, Paul E., Keller, Susanna R., Croniger, Colleen M., Kordula, Tomasz and Larner, Andrew C. 2012, Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity, Cell metabolism, vol. 16, no. 6, pp. 814-824, doi: 10.1016/j.cmet.2012.11.005.

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Title Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity
Author(s) Derecka, Marta
Gornicka, Agnieszka
Koralov, Sergei B.
Szczepanek, Karol
Morgan, Magdalena
Raje, Vicisha
Sisler, Jennifer
Zhang, Qifang
Otero, Dennis
Cichy, Joanna
Rajewsky, Klaus
Shimoda, Kazuya
Poli, Valeria
Strobl, Birgit
Pellegrini, Sandra
Harris, Thurl E.
Seale, Patrick
Russell, Aaron P.ORCID iD for Russell, Aaron P. orcid.org/0000-0002-7323-9501
McAinch, Andrew J.
O'Brien, Paul E.
Keller, Susanna R.
Croniger, Colleen M.
Kordula, Tomasz
Larner, Andrew C.
Journal name Cell metabolism
Volume number 16
Issue number 6
Start page 814
End page 824
Total pages 11
Publisher Cell Press
Place of publication Cambridge, Mass.
Publication date 2012-12-05
ISSN 1550-4131
Keyword(s) insulin
Prdm16 protein
protein kinase TYK2
regulator protein
STAT3 protein
unclassified drug
Summary 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.
Language eng
DOI 10.1016/j.cmet.2012.11.005
Field of Research 111603 Systems Physiology
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2012, Elsevier
Persistent URL http://hdl.handle.net/10536/DRO/DU:30050521

Document type: Journal Article
Collections: Faculty of Health
School of Exercise and Nutrition Sciences
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