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

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...

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Autores principales: 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, Chung, Choon Hee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Biochemistry and Molecular Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490079/
https://www.ncbi.nlm.nih.gov/pubmed/22824914
http://dx.doi.org/10.3858/emm.2012.44.10.066
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author 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
Chung, Choon Hee
author_facet 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
Chung, Choon Hee
author_sort Lee, Mi Young
collection PubMed
description 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.
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spelling pubmed-34900792012-11-07 Peroxisome proliferator-activated receptor δ agonist attenuates hepatic steatosis by anti-inflammatory mechanism 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 Chung, Choon Hee Exp Mol Med Original Article 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. Korean Society for Biochemistry and Molecular Biology 2012-10-31 2012-07-24 /pmc/articles/PMC3490079/ /pubmed/22824914 http://dx.doi.org/10.3858/emm.2012.44.10.066 Text en Copyright © 2012 by the Korean Society for Biochemistry and Molecular Biology http://creativecommons.org/licenses/by-nc/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
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
Chung, Choon Hee
Peroxisome proliferator-activated receptor δ agonist attenuates hepatic steatosis by anti-inflammatory mechanism
title Peroxisome proliferator-activated receptor δ agonist attenuates hepatic steatosis by anti-inflammatory mechanism
title_full Peroxisome proliferator-activated receptor δ agonist attenuates hepatic steatosis by anti-inflammatory mechanism
title_fullStr Peroxisome proliferator-activated receptor δ agonist attenuates hepatic steatosis by anti-inflammatory mechanism
title_full_unstemmed Peroxisome proliferator-activated receptor δ agonist attenuates hepatic steatosis by anti-inflammatory mechanism
title_short Peroxisome proliferator-activated receptor δ agonist attenuates hepatic steatosis by anti-inflammatory mechanism
title_sort peroxisome proliferator-activated receptor δ agonist attenuates hepatic steatosis by anti-inflammatory mechanism
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490079/
https://www.ncbi.nlm.nih.gov/pubmed/22824914
http://dx.doi.org/10.3858/emm.2012.44.10.066
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