Peroxisome proliferator-activated receptor delta agonist attenuates hepatic steatosis by anti-inflammatory mechanism
- 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.
- All Author(s)
- M. Y. Lee
; R. Choi
; H. M. Kim
; E. J. Cho
; B. H. Kim
; Y. S. Choi
; J. Naowaboot
; E. Y. Lee
; Y. C. Yang
; J. Y. Shin
; Y. G. Shin
; C. H. Chung
- Issued Date
- 2012
- Type
- Article
- Keyword
- diabetes mellitus; fatty liver; GW0742; inflammation; monocyte chemo-attractant protein-1; PPAR δ; PPARGC1A protein, human; tumor necrosis factor-α
- Publisher
- 생화학분자생물학회
- ISSN
- 1226-3613
- Citation Title
- Experimental & Molecular Medicine
- Citation Volume
- 44
- Citation Number
- 10
- Citation Start Page
- 578
- Citation End Page
- 585
- Language(ISO)
- eng
- DOI
- 10.3858/emm.2012.44.10.066
- URI
- http://schca-ir.schmc.ac.kr/handle/2022.oak/2661
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