Int J Med Sci 2016; 13(3):169-178. doi:10.7150/ijms.13581 This issue Cite

Research Paper

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

Hitoshi Maruyama, Soichiro Kiyono, Takayuki Kondo, Tadashi Sekimoto, Osamu Yokosuka

Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan

Citation:
Maruyama H, Kiyono S, Kondo T, Sekimoto T, Yokosuka O. Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease. Int J Med Sci 2016; 13(3):169-178. doi:10.7150/ijms.13581. https://www.medsci.org/v13p0169.htm
Other styles

File import instruction

Abstract

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.

Keywords: Palmitate, peroxisome proliferator-activated receptor γ, peroxisome proliferator-activated receptor coactivator 1 α, triglyceride, liver, nonalcoholic fatty liver disease


Citation styles

APA
Maruyama, H., Kiyono, S., Kondo, T., Sekimoto, T., Yokosuka, O. (2016). Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease. International Journal of Medical Sciences, 13(3), 169-178. https://doi.org/10.7150/ijms.13581.

ACS
Maruyama, H.; Kiyono, S.; Kondo, T.; Sekimoto, T.; Yokosuka, O. Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease. Int. J. Med. Sci. 2016, 13 (3), 169-178. DOI: 10.7150/ijms.13581.

NLM
Maruyama H, Kiyono S, Kondo T, Sekimoto T, Yokosuka O. Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease. Int J Med Sci 2016; 13(3):169-178. doi:10.7150/ijms.13581. https://www.medsci.org/v13p0169.htm

CSE
Maruyama H, Kiyono S, Kondo T, Sekimoto T, Yokosuka O. 2016. Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease. Int J Med Sci. 13(3):169-178.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
Popup Image