| First Author | Jung YS | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 7 | Pages | e0159425 |
| PubMed ID | 27455076 | Mgi Jnum | J:249312 |
| Mgi Id | MGI:6094537 | Doi | 10.1371/journal.pone.0159425 |
| Citation | Jung YS, et al. (2016) The Orphan Nuclear Receptor ERRgamma Regulates Hepatic CB1 Receptor-Mediated Fibroblast Growth Factor 21 Gene Expression. PLoS One 11(7):e0159425 |
| abstractText | 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) gamma increased FGF21 gene expression and secretion both in hepatocytes and mice, whereas knockdown of ERRgamma decreased ACEA-mediated FGF21 gene expression and secretion. Moreover, ERRgamma, but not ERRalpha and ERRbeta, induced FGF21 gene promoter activity. In addition, deletion and mutation analysis of the FGF21 promoter identified a putative ERRgamma-binding motif (AGGTGC, a near-consensus response element). A chromatin immunoprecipitation assay revealed direct binding of ERRgamma to the FGF21 gene promoter. Finally, GSK5182, an ERRgamma inverse agonist, significantly inhibited hepatic CB1 receptor-mediated FGF21 gene expression and secretion. CONCLUSION: Based on our data, we conclude that ERRgamma plays a key role in hepatic CB1 receptor-mediated induction of FGF21 gene expression and secretion. |
