title: Peroxisome proliferator-activated receptor δ agonist attenuates hepatic steatosis by anti-inflammatory mechanism.
abstract: Although peroxisome proliferator receptor (PPAR)-α and PPAR-γ agonist have been developed as chemical tools to uncover biological roles for the PPARs such as lipid and carbohydrate metabolism, PPAR-δ has not been fully investigated. In this study, we examined the effects of the PPAR-δ agonist GW0742 on fatty liver changes and inflammatory markers. We investigated the effects of PPAR-δ agonist GW0742 on fatty liver changes in OLETF rats. Intrahepatic triglyceride contents and expression of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1) and also, PPAR-γ coactivator (PGC)-1α gene were evaluated in liver tissues of OLETF rats and HepG2 cells after GW0742 treatment. The level of TNF-α 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-α, MCP-1, and PGC-1α 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 Raw264.7 cells. The expression level of Akt and IRS-1 was significantly increased by treatment with GW0742. The PPAR-δ agonist may attenuate hepatic fat accumulation through anti-inflammatory mechanism, reducing hepatic PGC-1α gene expression, and improvement of insulin signaling.
authors: Department of Internal Medicine, Korea Institute of Lifestyle Medicine Yonsei University Wonju College of Medicine Wonju 220-701,  Korea.
authors: Mi Young
authors: MY
authors: Lee
authors: Ran
authors: R
authors: Choi
authors: Hong Min
authors: HM
authors: Kim
authors: Eun Ju
authors: EJ
authors: Cho
authors: Bo Hwan
authors: BH
authors: Kim
authors: Yeon Sik
authors: YS
authors: Choi
authors: Jarinyaporn
authors: J
authors: Naowaboot
authors: Eun Young
authors: EY
authors: Lee
authors: Young Chul
authors: YC
authors: Yang
authors: Jang Yel
authors: JY
authors: Shin
authors: Young Goo
authors: YG
authors: Shin
authors: Choon Hee
authors: CH
authors: Chung
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood / Q000276:immunology / Q000378:metabolism; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D005951:Glucose Tolerance Test; D056945:Hep G2 Cells; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D047494:PPAR delta / Q000819:agonists* / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014280:Triglycerides / Q000378:metabolism; D010636:Phenols; D013438:Sulfhydryl Compounds
chemical_list: D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D016207:Cytokines; D047494:PPAR delta; D013844:Thiazoles; D014280:Triglycerides; C479979:(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid; D010636:Phenols; D013438:Sulfhydryl Compounds