GPR119: a promising target for nonalcoholic fatty liver disease
- Authors
- Yang, Jin Won; Kim, Hyo Seon; Im, Ji Hye; Kim, Ji Won; Jun, Dae Won; Lim, Sung Chul; Lee, Kyeong; Choi, Jong Min; Kim, Sang Kyum; Kang, Keon Wook
- Issue Date
- Jan-2016
- Publisher
- FEDERATION AMER SOC EXP BIOL
- Keywords
- AMPK; SREBP-1; steatosis
- Citation
- FASEB JOURNAL, v.30, no.1, pp.324 - 335
- Indexed
- SCIE
SCOPUS
- Journal Title
- FASEB JOURNAL
- Volume
- 30
- Number
- 1
- Start Page
- 324
- End Page
- 335
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/24085
- DOI
- 10.1096/fj.15-273771
- ISSN
- 0892-6638
- 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.
- Files in This Item
-
Go to Link
- Appears in
Collections - 서울 의과대학 > 서울 내과학교실 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/24085)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.