Peroxisome proliferator-activated receptor δ agonist attenuates hepatic steatosis by anti-inflammatory mechanism

Choon Hee Chung, Mi Young Lee, Ran Choi, Hong Min Kim, Eun Ju Cho, Bo Hwan Kim, Yeon Sik Choi, Jarinyaporn Naowaboot, Eun Young Lee, Young Chul Yang, Jang Yel Shin, Young Goo Shin

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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.

Original languageEnglish
Pages (from-to)578-585
Number of pages8
JournalExperimental and Molecular Medicine
Volume44
Issue number10
DOIs
Publication statusPublished - 2012 Oct 31

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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    Chung, C. H., Lee, M. Y., Choi, R., Kim, H. M., Cho, E. J., Kim, B. H., Choi, Y. S., Naowaboot, J., Lee, E. Y., Yang, Y. C., Shin, J. Y., & Shin, Y. G. (2012). Peroxisome proliferator-activated receptor δ agonist attenuates hepatic steatosis by anti-inflammatory mechanism. Experimental and Molecular Medicine, 44(10), 578-585. https://doi.org/10.3858/emm.2012.44.10.066