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 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.
['Maruyama|Hitoshi|H|', 'Kiyono|Soichiro|S|', 'Kondo|Takayuki|T|', 'Sekimoto|Tadashi|T|', 'Yokosuka|Osamu|O|']
D000818:Animals D002460:Cell Line D004195:Disease Models, Animal D005786:Gene Expression Regulation D050356:Lipid Metabolism D008099:Liver D008297:Male D008815:Mice, Inbred Strains D065626:Non-alcoholic Fatty Liver Disease D019301:Oleic Acid D047495:PPAR gamma D010168:Palmitates D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha D014280:Triglycerides D015854:Up-Regulation
liver nonalcoholic fatty liver disease Palmitate triglyceride peroxisome proliferator-activated receptor coactivator 1 α peroxisome proliferator-activated receptor γ