title: Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Derecka
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gornicka
authors.forename: Sergei B
authors.initials: SB
authors.lastname: Koralov
authors.forename: Karol
authors.initials: K
authors.lastname: Szczepanek
authors.forename: Magdalena
authors.initials: M
authors.lastname: Morgan
authors.forename: Vidisha
authors.initials: V
authors.lastname: Raje
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sisler
authors.forename: Qifang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Dennis
authors.initials: D
authors.lastname: Otero
authors.forename: Joanna
authors.initials: J
authors.lastname: Cichy
authors.forename: Klaus
authors.initials: K
authors.lastname: Rajewsky
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimoda
authors.forename: Valeria
authors.initials: V
authors.lastname: Poli
authors.forename: Birgit
authors.initials: B
authors.lastname: Strobl
authors.forename: Sandra
authors.initials: S
authors.lastname: Pellegrini
authors.forename: Thurl E
authors.initials: TE
authors.lastname: Harris
authors.forename: Patrick
authors.initials: P
authors.lastname: Seale
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Russell
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McAinch
authors.forename: Paul E
authors.initials: PE
authors.lastname: O'Brien
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Keller
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Croniger
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kordula
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Larner
mesh_terms: D002001:Adipose Tissue, Brown / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007328:Insulin; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D053634:TYK2 Kinase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015431:Weight Loss
chemical_list: D004268:DNA-Binding Proteins; D007328:Insulin; C521133:Prdm16 protein, mouse; D050796:STAT3 Transcription Factor; D014157:Transcription Factors; D053634:TYK2 Kinase