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Title 

The orphan nuclear receptor ERRγ regulates hepatic CB1 receptor-mediated fibroblast growth factor 21 gene expression

Authors 

Y S JungJ M LeeD K KimY S LeeK S KimYong-Hoon KimJ KimM S LeeI K LeeS H KimS J ChoW I JeongChul Ho LeeR HarrisH S Choi

Publisher 

Public Library of Science

Issue Date 

2016

Citation 

Plos One, vol. 11, no. 7, pp. e01594-e01594

Abstract 

Background Fibroblast growth factor 21 (FGF21), a stress inducible hepatokine, is synthesized in the liver and plays important roles in glucose and lipid metabolism. However, the mechanism of hepatic cannabinoid type 1 (CB1) receptor-mediated induction of FGF21 gene expression is largely unknown. Results Activation of the hepatic CB1 receptor by arachidonyl-2'-chloroethylamide (ACEA), a CB1 receptor selective agonist, significantly increased FGF21 gene expression. Overexpression of estrogen-related receptor (ERR) γ increased FGF21 gene expression and secretion both in hepatocytes and mice, whereas knockdown of ERRγ decreased ACEA-mediated FGF21 gene expression and secretion. Moreover, ERRγ , but not ERRα and ERRβ, induced FGF21 gene promoter activity. In addition, deletion and mutation analysis of the FGF21 promoter identified a putative ERRγ -binding motif (AGGTGC, a near-consensus response element). A chromatin immunoprecipitation assay revealed direct binding of ERRγ to the FGF21 gene promoter. Finally, GSK5182, an ERRγ inverse agonist, significantly inhibited hepatic CB1 receptor-mediated FGF21 gene expression and secretion. Conclusion Based on our data, we conclude that ERRγ plays a key role in hepatic CB1 receptor-mediated induction of FGF21 gene expression and secretion.

ISSN 

1932-6203

Link 

http://dx.doi.org/10.1371/journal.pone.0159425

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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