Peroxisome proliferator-activated receptor delta agonist attenuates hepatic steatosis by anti-inflammatory mechanism
- Authors
- Lee, Mi Young; Choi, Ran; Kim, Hong Min; Cho, Eun Ju; Kim, Bo Hwan; Choi, Yeon Sik; Naowaboot, Jarinyaporn; Lee, Eun Young; Yang, Young Chul; Shin, Jang Ye; Shin, Young Goo; Chung, Choon Hee
- Issue Date
- 31-Oct-2012
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- diabetes mellitus; fatty liver; GW0742; inflammation; monocyte chemo-attractant protein-1; PPAR delta; PPARGC1A protein, human; tumor necrosis factor-alpha
- Citation
- EXPERIMENTAL AND MOLECULAR MEDICINE, v.44, no.10, pp.578 - 585
- Journal Title
- EXPERIMENTAL AND MOLECULAR MEDICINE
- Volume
- 44
- Number
- 10
- Start Page
- 578
- End Page
- 585
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/16071
- DOI
- 10.3858/emm.2012.44.10.066
- ISSN
- 1226-3613
- Abstract
- Although peroxisome proliferator receptor (PPAR)-alpha and PPAR-gamma agonist have been developed as chemical tools to uncover biological roles for the PPARs such as lipid and carbohydrate metabolism, PPAR-delta has not been fully investigated. In this study, we examined the effects of the PPAR-delta agonist GW0742 on fatty liver changes and inflammatory markers. We investigated the effects of PPAR-delta agonist GW0742 on fatty liver changes in OLETF rats. Intrahepatic triglyceride contents and expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and monocyte chemo-attractant protein-1 (MCP-1) and also, PPAR-gamma coactivator (PGC)-1 alpha gene were evaluated in liver tissues of OLETF rats and HepG2 cells after GW0742 treatment. The level of TNF-alpha and MCP-1 was also examined in supernatant of Raw264. 7 cell culture. To address the effects of GW0742 on insulin signaling, we performed in vitro study with AML12 mouse hepatocytes. Rats treated with GW0742 (10 mg/kg/day) from 26 to 36 weeks showed improvement in fatty infiltration of the liver. In liver tissues, mRNA expressions of TNF-alpha, MCP-1, and PGC-1 alpha were significantly decreased in diabetic rats treated with GW0742 compared to diabetic control rats. We also observed that GW0742 had inhibitory effects on palmitic acid-induced fatty accumulation and inflammatory markers in HepG2 and Ravv264.7 cells. The expression level of Akt and IRS-1 was significantly increased by treatment with GW0742. The PPAR-delta agonist may attenuate hepatic fat accumulation through anti-inflammatory mechanism, reducing hepatic PGC-1 alpha gene expression, and improvement of insulin signaling.
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