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The Orphan Nuclear Receptor ERRγ Regulates Hepatic CB1 Receptor-Mediated Fibroblast Growth Factor 21 Gene Expression

DC Field Value Language
dc.contributor.author이명식-
dc.date.accessioned2017-10-26T07:24:13Z-
dc.date.available2017-10-26T07:24:13Z-
dc.date.issued2016-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/151983-
dc.description.abstractBACKGROUND: 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.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherPublic Library of Science-
dc.relation.isPartOfPLOS ONE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHCell Line-
dc.subject.MESHFibroblast Growth Factors/genetics*-
dc.subject.MESHGene Expression Regulation*/drug effects-
dc.subject.MESHGene Knockdown Techniques-
dc.subject.MESHHepatocytes/metabolism*-
dc.subject.MESHHumans-
dc.subject.MESHMale-
dc.subject.MESHMice-
dc.subject.MESHMice, Knockout-
dc.subject.MESHOrphan Nuclear Rceptors/genetics-
dc.subject.MESHOrphan Nuclear Receptors/metabolism*-
dc.subject.MESHPromoter Regions, Genetic-
dc.subject.MESHRNA, Messenger/genetics-
dc.subject.MESHRNA, Messenger/metabolism-
dc.subject.MESHReceptor, Cannabinoid, CB1/agonists-
dc.subject.MESHReceptor, Cannabinoid, CB1/metabolism*-
dc.subject.MESHReceptors, Estrogen/genetics-
dc.subject.MESHReceptors, Estrogen/metabolism*-
dc.subject.MESHTamoxifen/analogs & derivatives-
dc.subject.MESHTamoxifen/pharmacology-
dc.titleThe Orphan Nuclear Receptor ERRγ Regulates Hepatic CB1 Receptor-Mediated Fibroblast Growth Factor 21 Gene Expression-
dc.typeArticle-
dc.publisher.locationUnited States-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Life Science-
dc.contributor.googleauthorYoon Seok Jung-
dc.contributor.googleauthorJi-Min Lee-
dc.contributor.googleauthorDon-Kyu Kim-
dc.contributor.googleauthorYong-Soo Lee-
dc.contributor.googleauthorKi-Sun Kim-
dc.contributor.googleauthorYong-Hoon Kim-
dc.contributor.googleauthorJina Kim-
dc.contributor.googleauthorMyung-Shik Lee-
dc.contributor.googleauthorIn-Kyu Lee-
dc.contributor.googleauthorSeong Heon Kim-
dc.contributor.googleauthorSung Jin Cho-
dc.contributor.googleauthorWon-Il Jeong-
dc.contributor.googleauthorChul-Ho Lee-
dc.contributor.googleauthorRobert A. Harris-
dc.contributor.googleauthorHueng-Sik Choi-
dc.identifier.doi10.1371/journal.pone.0159425-
dc.contributor.localIdA02752-
dc.relation.journalcodeJ02540-
dc.identifier.eissn1932-6203-
dc.identifier.pmid27455076-
dc.contributor.alternativeNameLee, Myung Shik-
dc.contributor.affiliatedAuthorLee, Myung Shik-
dc.citation.volume11-
dc.citation.number7-
dc.citation.startPagee0159425-
dc.identifier.bibliographicCitationPLOS ONE, Vol.11(7) : e0159425, 2016-
dc.date.modified2017-10-24-
dc.identifier.rimsid46305-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers

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