The Effects of PGC-1α on Diet-Induced Insulin Resistance

學生姓名: 龍秉廷
指導教授: 龔瑞林
學  號: 10332017
學期: 130上
摘  要: High fat diet (HFD) -induced insulin resistance (IR) is partially characterized by reduced skeletal muscle mitochondrial function and peroxisome proliferator activated receptor gamma coactivator 1-α (PGC-1α) expression. PGC-1α is a transcriptional regulator which control the expression of genes involved in energy homeostasis, mitochondrial biogenesis, fatty acid oxidation and glucose metabolism. The aim of this study was to investigate the PGC-1α signaling on diet-induced obesity. First the study evaluated the effects of pre-diabetes on testicular expression of PGC-1α and its downstream gene on testicular mitochondrial bioenergetics. The results showed that high energy diet-induced pre-diabetes down regulated both PGC-1α and Sirtuin3 protein expression, and that might impair testicular electron transport chain function. Secondly, by generating PGC-1α overexpression transgenic (TG) mice, the evidences indicated that overexpression of PGC-1α has a negative effect on hepatic insulin sensitivity but it improved insulin action in muscle. Thirdly, quercetin, an abundant bioflavonoid in apples, onions and tea, is a powerful antioxidant that has the potential to improve insulin action and skeletal muscle mitochondrial biogenesis. Under different doses of quercetin to HFD-induced mice the results demonstrated that dietary quercetin supplementation at 50 μg per mouse per day ameliorated the development of diet-induced IR as well as increasing PGC-1α expression in muscle. In conclusion, PGC-1α may improve HFD-induced IR through regulating mitochondrial function.