Peroxisome proliferator-activated receptor delta agonist attenuates hepatic steatosis by anti-inflammatory mechanism
Experimental & Molecular Medicine
;
: 578-585, 2012.
Artigo
em Inglês
| WPRIM
| ID: wpr-14965
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)-1alpha 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-1alpha 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-delta agonist may attenuate hepatic fat accumulation through anti-inflammatory mechanism, reducing hepatic PGC-1alpha gene expression, and improvement of insulin signaling.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Tiazóis
/
Triglicerídeos
/
Glicemia
/
Resistência à Insulina
/
Citocinas
/
Ratos Long-Evans
/
PPAR delta
/
Diabetes Mellitus
/
Fígado Gorduroso
/
Células Hep G2
Limite:
Animais
/
Humanos
/
Masculino
Idioma:
Inglês
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2012
Tipo de documento:
Artigo
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