Pyruvate kinase M2 represses thermogenic gene expression in brown adipocytes

FEBS Letters

article

Marie S. Isidor¹  Sally Winther¹  Lasse K. Markussen¹  Astrid L. Basse¹  Bjørn Quistorff²  Jan Nedergaard³  Brice Emanuelli⁴  Jacob B. Hansen¹ 

[1] Department of Biology, University of Copenhagen;Department of Biomedical Sciences, University of Copenhagen;Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University;Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen

关键词: brown adipose tissue;    Fgf21;    glycolysis;    metabolism;    obesity;    pyruvate kinase;    thermogenesis;    Ucp1;   

DOI  :  10.1002/1873-3468.13716

来源: John Wiley & Sons Ltd.

【 摘 要 】

Utilizing the thermogenic capacity of brown adipose tissue is a potential antiobesity strategy; therefore, the mechanisms controlling expression of thermogenesis-related genes are of interest. Pyruvate kinase (PK) catalyzes the last step of glycolysis and exists as four isoenzymes: PK, liver, PK, red blood cell, PK, muscle (PKM1 and PKM2). PKM2 has both glycolytic and nuclear functions. Here, we report that PKM2 is enriched in brown adipose compared with white adipose tissue. Specific knockdown of PKM2 in mature brown adipocytes demonstrates that silencing of PKM2 does not lead to a decrease in PK activity, but causes a robust upregulation of thermogenic uncoupling protein 1 (Ucp1) and fibroblast growth factor 21 (Fgf21) gene expression. This increase is not mediated by any of the known mechanisms for PKM2- regulated gene expression, thus implying the existence of a novel mechanism for PKM2-dependent effects on gene expression.

【 授权许可】

Unknown