Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity

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; A J McAinch; Paul Edmond O'Brien; Susanna R Keller; Colleen M Croniger; Tomasz Kordula; Andrew C Larner

doi:10.1016/j.cmet.2012.11.005

Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity

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, A J McAinch, Paul Edmond O'BrienSusanna R Keller, Colleen M Croniger, Tomasz Kordula, Andrew C Larner

Research output: Contribution to journal › Article › Research › peer-review

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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.

Original language	English
Pages (from-to)	814 - 824
Number of pages	11
Journal	Cell Metabolism
Volume	16
Issue number	6
DOIs	https://doi.org/10.1016/j.cmet.2012.11.005
Publication status	Published - 2012

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SDG 3 Good Health and Well-being

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10.1016/j.cmet.2012.11.005

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Derecka, M., Gornicka, A., Koralov, S. B., Szczepanek, K., Morgan, M., Raje, V., Sisler, J., Zhang, Q., Otero, D., Cichy, J., Rajewsky, K., Shimoda, K., Poli, V., Strobl, B., Pellegrini, S., Harris, T. E., Seale, P., Russell, A. P., McAinch, A. J., ... Larner, A. C. (2012). Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity. Cell Metabolism, 16(6), 814 - 824. https://doi.org/10.1016/j.cmet.2012.11.005

@article{e9226a76224847949682ccb370456639,

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.",

author = "Marta Derecka and Agnieszka Gornicka and Koralov, \{Sergei B\} and Karol Szczepanek and Magdalena Morgan and Vidisha Raje and Jennifer Sisler and Qifang Zhang and Dennis Otero and Joanna Cichy and Klaus Rajewsky and Kazuya Shimoda and Valeria Poli and Birgit Strobl and Sandra Pellegrini and Harris, \{Thurl E\} and Patrick Seale and Russell, \{Aaron P\} and McAinch, \{A J\} and O'Brien, \{Paul Edmond\} and Keller, \{Susanna R\} and Croniger, \{Colleen M\} and Tomasz Kordula and Larner, \{Andrew C\}",

year = "2012",

doi = "10.1016/j.cmet.2012.11.005",

language = "English",

volume = "16",

pages = "814 -- 824",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Elsevier",

number = "6",

}

Derecka, M, Gornicka, A, Koralov, SB, Szczepanek, K, Morgan, M, Raje, V, Sisler, J, Zhang, Q, Otero, D, Cichy, J, Rajewsky, K, Shimoda, K, Poli, V, Strobl, B, Pellegrini, S, Harris, TE, Seale, P, Russell, AP, McAinch, AJ, O'Brien, PE, Keller, SR, Croniger, CM, Kordula, T & Larner, AC 2012, 'Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity', Cell Metabolism, vol. 16, no. 6, pp. 814 - 824. https://doi.org/10.1016/j.cmet.2012.11.005

TY - JOUR

T1 - Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity

AU - Derecka, Marta

AU - Gornicka, Agnieszka

AU - Koralov, Sergei B

AU - Szczepanek, Karol

AU - Morgan, Magdalena

AU - Raje, Vidisha

AU - Sisler, Jennifer

AU - Zhang, Qifang

AU - Otero, Dennis

AU - Cichy, Joanna

AU - Rajewsky, Klaus

AU - Shimoda, Kazuya

AU - Poli, Valeria

AU - Strobl, Birgit

AU - Pellegrini, Sandra

AU - Harris, Thurl E

AU - Seale, Patrick

AU - Russell, Aaron P

AU - McAinch, A J

AU - O'Brien, Paul Edmond

AU - Keller, Susanna R

AU - Croniger, Colleen M

AU - Kordula, Tomasz

AU - Larner, Andrew C

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

UR - http://www.sciencedirect.com/science/article/pii/S1550413112004585

UR - https://www.scopus.com/pages/publications/84870484174

U2 - 10.1016/j.cmet.2012.11.005

DO - 10.1016/j.cmet.2012.11.005

M3 - Article

SN - 1550-4131

VL - 16

SP - 814

EP - 824

JO - Cell Metabolism

JF - Cell Metabolism

IS - 6

ER -

Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity

Abstract

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