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dc.contributor.author전대원-
dc.date.accessioned2017-11-09T05:40:23Z-
dc.date.available2017-11-09T05:40:23Z-
dc.date.issued2016-01-
dc.identifier.citationFASEB JOURNAL, v. 30, NO 1, Page. 324-335en_US
dc.identifier.issn0892-6638-
dc.identifier.issn1530-6860-
dc.identifier.urihttp://www.fasebj.org/content/30/1/324-
dc.identifier.urihttp://hdl.handle.net/20.500.11754/30609-
dc.description.abstractNonalcoholic fatty liver disease is associated with metabolic syndrome and has the unique characteristic of excess lipid accumulation in liver. G-protein-coupled receptor 119 (GPR119) is a promising target for type 2 diabetes. However, the role of GPR119 activation in hepatic steatosis and its precise mechanism has not been investigated. In primary cultured hepatocytes from wild-type and GPR119 knockout (KO) mice, expression of lipogenic enzymes was elevated in GPR119 KO hepatocytes. Treatment of hepatocytes and HepG2 cells with GPR119 agonists in phase 2 clinical trials (MBX-2982 [MBX] and GSK1292263) inhibited protein expression of both nuclear and total sterol regulatory element binding protein (SREBP)-1, a key lipogenesis transcription factor. Oral administration of MBX in mice fed a high-fat diet potently inhibited hepatic lipid accumulation and expression levels of SREBP-1 and lipogenesis-related genes, whereas the hepatic antilipogenesis effects of MBX were abolished in GPR119 KO mice. MBX activated AMPK and increased Ser-372 phosphorylation of SREBP-1c, an inhibitory form of SREBP-1c. Moreover, inhibition of AMPK recovered MBX-induced down-regulation of SREBP-1. These findings demonstrate for the first time that the GPR119 ligand alleviates hepatic steatosis by inhibiting SREBP-1-mediated lipogenesis in hepatocytes.en_US
dc.description.sponsorshipThe authors acknowledge financial support from the National Research Foundation of Korea, funded by the Korean government (2014M3A9A8064408, 2012M3A9C1053532, and 2007-005681).en_US
dc.language.isoenen_US
dc.publisherFEDERATION AMER SOC EXP BIOLen_US
dc.subjectAMPKen_US
dc.subjectSREBP-1en_US
dc.subjectsteatosisen_US
dc.titleGPR119: a promising target for nonalcoholic fatty liver diseaseen_US
dc.typeArticleen_US
dc.relation.no1-
dc.relation.volume30-
dc.identifier.doi10.1096/fj.15-273771-
dc.relation.page324-335-
dc.relation.journalFASEB JOURNAL-
dc.contributor.googleauthorYang, Jin Won-
dc.contributor.googleauthorKim, Hyo Seon-
dc.contributor.googleauthorIm, Ji Hye-
dc.contributor.googleauthorKim, Ji Won-
dc.contributor.googleauthorJun, Dae Won-
dc.contributor.googleauthorLim, Sung Chul-
dc.contributor.googleauthorLee, Kyeong-
dc.contributor.googleauthorChoi, Jong Min-
dc.contributor.googleauthorKim, Sang Kyum-
dc.contributor.googleauthorKang, Keon Wook-
dc.relation.code2016000515-
dc.sector.campusS-
dc.sector.daehakCOLLEGE OF MEDICINE[S]-
dc.sector.departmentDEPARTMENT OF MEDICINE-
dc.identifier.pidnoshin-
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COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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