GPR119: a promising target for nonalcoholic fatty liver disease
DC Field | Value | Language |
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dc.contributor.author | Yang, Jin Won | - |
dc.contributor.author | Kim, Hyo Seon | - |
dc.contributor.author | Im, Ji Hye | - |
dc.contributor.author | Kim, Ji Won | - |
dc.contributor.author | Jun, Dae Won | - |
dc.contributor.author | Lim, Sung Chul | - |
dc.contributor.author | Lee, Kyeong | - |
dc.contributor.author | Choi, Jong Min | - |
dc.contributor.author | Kim, Sang Kyum | - |
dc.contributor.author | Kang, Keon Wook | - |
dc.date.accessioned | 2021-08-02T17:36:04Z | - |
dc.date.available | 2021-08-02T17:36:04Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2016-01 | - |
dc.identifier.issn | 0892-6638 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/24085 | - |
dc.description.abstract | Nonalcoholic 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. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | FEDERATION AMER SOC EXP BIOL | - |
dc.title | GPR119: a promising target for nonalcoholic fatty liver disease | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Jun, Dae Won | - |
dc.identifier.doi | 10.1096/fj.15-273771 | - |
dc.identifier.scopusid | 2-s2.0-84973495988 | - |
dc.identifier.wosid | 000367621000031 | - |
dc.identifier.bibliographicCitation | FASEB JOURNAL, v.30, no.1, pp.324 - 335 | - |
dc.relation.isPartOf | FASEB JOURNAL | - |
dc.citation.title | FASEB JOURNAL | - |
dc.citation.volume | 30 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 324 | - |
dc.citation.endPage | 335 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Life Sciences & Biomedicine - Other Topics | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | ACTIVATED PROTEIN-KINASE | - |
dc.subject.keywordPlus | GLUCAGON-LIKE PEPTIDE-1 | - |
dc.subject.keywordPlus | HEPATIC STEATOSIS | - |
dc.subject.keywordPlus | COUPLED RECEPTOR | - |
dc.subject.keywordPlus | GLYCEMIC CONTROL | - |
dc.subject.keywordPlus | X RECEPTORS | - |
dc.subject.keywordPlus | INSULIN | - |
dc.subject.keywordPlus | AMPK | - |
dc.subject.keywordPlus | GLUCOSE | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordAuthor | AMPK | - |
dc.subject.keywordAuthor | SREBP-1 | - |
dc.subject.keywordAuthor | steatosis | - |
dc.identifier.url | https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.15-273771 | - |
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