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Pyruvate kinase M2 represses thermogenic gene expression in brown adipocytes
Author(s) -
Isidor Marie S.,
Winther Sally,
Markussen Lasse K.,
Basse Astrid L.,
Quistorff Bjørn,
Nedergaard Jan,
Emanuelli Brice,
Hansen Jacob B.
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13716
Subject(s) - pkm2 , pyruvate kinase , brown adipose tissue , thermogenesis , fgf21 , gene knockdown , adipose tissue , glycolysis , thermogenin , gene expression , gene silencing , biology , white adipose tissue , chemistry , microbiology and biotechnology , biochemistry , gene , fibroblast growth factor , metabolism , receptor
Utilizing the thermogenic capacity of brown adipose tissue is a potential anti‐obesity 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.