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 language | English |
|---|---|
| Pages (from-to) | 578-585 |
| Number of pages | 8 |
| Journal | Experimental and Molecular Medicine |
| Volume | 44 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2012 Oct 31 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry
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Peroxisome proliferator-activated receptor δ agonist attenuates hepatic steatosis by anti-inflammatory mechanism. / Chung, Choon Hee; 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 Yel; Shin, Young Goo.
In: Experimental and Molecular Medicine, Vol. 44, No. 10, 31.10.2012, p. 578-585.Research output: Contribution to journal › Article
TY - JOUR
T1 - Peroxisome proliferator-activated receptor δ agonist attenuates hepatic steatosis by anti-inflammatory mechanism
AU - Chung, Choon Hee
AU - Lee, Mi Young
AU - Choi, Ran
AU - Kim, Hong Min
AU - Cho, Eun Ju
AU - Kim, Bo Hwan
AU - Choi, Yeon Sik
AU - Naowaboot, Jarinyaporn
AU - Lee, Eun Young
AU - Yang, Young Chul
AU - Shin, Jang Yel
AU - Shin, Young Goo
PY - 2012/10/31
Y1 - 2012/10/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84868132548&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84868132548&partnerID=8YFLogxK
U2 - 10.3858/emm.2012.44.10.066
DO - 10.3858/emm.2012.44.10.066
M3 - Article
C2 - 22824914
AN - SCOPUS:84868132548
VL - 44
SP - 578
EP - 585
JO - Experimental and Molecular Medicine
JF - Experimental and Molecular Medicine
SN - 1226-3613
IS - 10
ER -