期刊
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
卷 13, 期 3, 页码 169-178出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijms.13581
关键词
Palmitate; peroxisome proliferator-activated receptor gamma; peroxisome proliferator-activated receptor coactivator 1 alpha; triglyceride; liver; nonalcoholic fatty liver disease
The aim was to examine the effect of free fatty acids on the regulation of PPAR gamma-PGC1 alpha pathway, and the effect of PPAR gamma/PGC1 alpha in NAFLD. The mRNA and protein expression of PGC1 alpha and phospho/total PPAR gamma 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 PGC1 alpha and PPAR gamma in the liver were examined in the control and NAFLD mice. Palmitate (500 mu M), but not oleate, increased protein expression of PGC1 alpha and phospho PPAR gamma (PGC1 alpha, 1.42-fold, P=0.038; phospho PPAR gamma, 1.56-fold, P=0.022). The palmitate-induced PPAR gamma mRNA expression was reduced after the transfection (0.46-fold), and the protein expressions of PGC1 alpha (0.52-fold, P=0.019) and phospho PPAR gamma (0.43-fold, P=0.011) were suppressed in siRNA-transfected cells. The palmitate (12325.8 +/- 1758.9 mu g/g vs. 6245.6 +/- 1182.7 mu g/g, p=0.002), and mRNA expression of PGC1 alpha (11.0 vs. 5.5, p=0.03) and PPAR. (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 PGC1 alpha and PPAR. were higher in the NAFLD group than in the controls (PGC1 alpha, 1.41-fold, P=0.035; PPAR gamma, 1.39-fold, P=0.042), and were higher in the high-triglyceride liver group (PGC1 alpha, 1.52-fold, p=0.03; PPAR gamma, 1.22-fold, p=0.05) than in the low-triglyceride liver group. In conclusion, palmitate appear to up-regulate PPAR gamma via PGC1 alpha in Huh7 cells, and both PGC1 alpha and PPAR gamma are up-regulated in the NAFLD mice liver, suggesting an effect on lipid metabolism leading to intrahepatic triglyceride accumulation.
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