Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease

The aim was to examine the effect of free fatty acids on the regulation of PPARγ-PGC1α pathway, and the effect of PPARγ/PGC1α in NAFLD. The mRNA and protein expression of PGC1α and phospho/total PPARγ were examined in Huh7 cells after the palmitate/oleate treatment with/without the transfection with...

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Main Authors:	Maruyama, Hitoshi, Kiyono, Soichiro, Kondo, Takayuki, Sekimoto, Tadashi, Yokosuka, Osamu
Format:	Online
Language:	English
Published:	Ivyspring International Publisher 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773281/

id	pubmed-4773281
recordtype	oai_dc
spelling	pubmed-47732812016-03-03 Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease Maruyama, Hitoshi Kiyono, Soichiro Kondo, Takayuki Sekimoto, Tadashi Yokosuka, Osamu Research Paper The aim was to examine the effect of free fatty acids on the regulation of PPARγ-PGC1α pathway, and the effect of PPARγ/PGC1α in NAFLD. The mRNA and protein expression of PGC1α and phospho/total PPARγ were examined in Huh7 cells after the palmitate/oleate treatment with/without the transfection with siRNA against PGC1a. The palmitate content, mRNA and protein expression of PGC1α and PPARγ in the liver were examined in the control and NAFLD mice. Palmitate (500 μM), but not oleate, increased protein expression of PGC1α and phospho PPARγ (PGC1α, 1.42-fold, P=0.038; phospho PPARγ, 1.56-fold, P=0.022). The palmitate-induced PPARγ mRNA expression was reduced after the transfection (0.46‑fold), and the protein expressions of PGC1α (0.52-fold, P=0.019) and phospho PPARγ (0.43-fold, P=0.011) were suppressed in siRNA-transfected cells. The palmitate (12325.8 ± 1758.9 μg/g vs. 6245.6 ± 1182.7 μg/g, p=0.002), and mRNA expression of PGC1α (11.0 vs. 5.5, p=0.03) and PPARγ (4.3 vs. 2.2, p=0.0001) in the liver were higher in high-triglyceride liver mice (>15.2 mg/g) than in low-triglyceride liver mice (<15.2 mg/g). The protein expressions of both PGC1α and PPARγ were higher in the NAFLD group than in the controls (PGC1α, 1.41-fold, P=0.035; PPARγ, 1.39-fold, P=0.042), and were higher in the high-triglyceride liver group (PGC1α, 1.52-fold, p=0.03; PPARγ, 1.22-fold, p=0.05) than in the low-triglyceride liver group. In conclusion, palmitate appear to up-regulate PPARγ via PGC1α in Huh7 cells, and both PGC1α and PPARγ are up-regulated in the NAFLD mice liver, suggesting an effect on lipid metabolism leading to intrahepatic triglyceride accumulation. Ivyspring International Publisher 2016-02-11 /pmc/articles/PMC4773281/ /pubmed/26941577 http://dx.doi.org/10.7150/ijms.13581 Text en © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Maruyama, Hitoshi Kiyono, Soichiro Kondo, Takayuki Sekimoto, Tadashi Yokosuka, Osamu
spellingShingle	Maruyama, Hitoshi Kiyono, Soichiro Kondo, Takayuki Sekimoto, Tadashi Yokosuka, Osamu Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease
author_facet	Maruyama, Hitoshi Kiyono, Soichiro Kondo, Takayuki Sekimoto, Tadashi Yokosuka, Osamu
author_sort	Maruyama, Hitoshi
title	Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease
title_short	Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease
title_full	Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease
title_fullStr	Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease
title_full_unstemmed	Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease
title_sort	palmitate-induced regulation of pparγ via pgc1α: a mechanism for lipid accumulation in the liver in nonalcoholic fatty liver disease
description	The aim was to examine the effect of free fatty acids on the regulation of PPARγ-PGC1α pathway, and the effect of PPARγ/PGC1α in NAFLD. The mRNA and protein expression of PGC1α and phospho/total PPARγ were examined in Huh7 cells after the palmitate/oleate treatment with/without the transfection with siRNA against PGC1a. The palmitate content, mRNA and protein expression of PGC1α and PPARγ in the liver were examined in the control and NAFLD mice. Palmitate (500 μM), but not oleate, increased protein expression of PGC1α and phospho PPARγ (PGC1α, 1.42-fold, P=0.038; phospho PPARγ, 1.56-fold, P=0.022). The palmitate-induced PPARγ mRNA expression was reduced after the transfection (0.46‑fold), and the protein expressions of PGC1α (0.52-fold, P=0.019) and phospho PPARγ (0.43-fold, P=0.011) were suppressed in siRNA-transfected cells. The palmitate (12325.8 ± 1758.9 μg/g vs. 6245.6 ± 1182.7 μg/g, p=0.002), and mRNA expression of PGC1α (11.0 vs. 5.5, p=0.03) and PPARγ (4.3 vs. 2.2, p=0.0001) in the liver were higher in high-triglyceride liver mice (>15.2 mg/g) than in low-triglyceride liver mice (<15.2 mg/g). The protein expressions of both PGC1α and PPARγ were higher in the NAFLD group than in the controls (PGC1α, 1.41-fold, P=0.035; PPARγ, 1.39-fold, P=0.042), and were higher in the high-triglyceride liver group (PGC1α, 1.52-fold, p=0.03; PPARγ, 1.22-fold, p=0.05) than in the low-triglyceride liver group. In conclusion, palmitate appear to up-regulate PPARγ via PGC1α in Huh7 cells, and both PGC1α and PPARγ are up-regulated in the NAFLD mice liver, suggesting an effect on lipid metabolism leading to intrahepatic triglyceride accumulation.
publisher	Ivyspring International Publisher
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773281/
_version_	1613545617494114304

Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease

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