Mechanisms of peroxisome proliferator-activated receptor gamma coactivator 1α in high-fat diet-induced skeletal muscle mitochondrial dysfunction in rats / 中华老年医学杂志

ABSTRACT

Objective To investigate the role of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) in high-fat diet-induced insulin resistance (IR) and mitochondrial degeneration in skeletal muscle.Methods Wistar rats were randomly divided into a normal chow (NC)group (n =10) and a high-fat diet(HFD)group (n =10).After eight weeks,fasting plasma glucose(FBG) levels,fasting insulin(FINS) levels and glucose infusion rates (GIR) in each group were measured (n=3).Samples of rat skeletal muscle were harvested.L6 myoblasts were divided into a control group,a PA group (cells were cultured in palmitic acid),a pcDNA3 group (cells were transfected by the plasmid pcDNA3)and a pcDNA3-PGC1α group (cells were transfected by the PGC1α-overexpressiorn plasmid).Expression levels of PGC1α,nuclear respiratory factor 1 (NRF1),uncoupling protein 3 (UCP3),and cytochrome C oxidase 1 (COX1) in skeletal muscle and L6 myoblasts were measured by real-time PCR and Western blotting.Results Levels of FBG and insulin were higher and those of GIR were lower in the HFD group than in the NC group,(6.0±0.7)mmol/L vs.(5.0±0.4)mmol/L、(23.3±3.0)mU/L vs.(12.9±1.8)mU/L、(14.2±1.8)％ vs.(22.6±2.4)％ (t =-3.578,-6.679,6.265,respectively,P ＜ 0.05).Expression levels of PGC1α,NRF1,UCP3,and COX1 were down in skeletal muscle in the HFD group compared with those in the NC group(P ＜0.05).In L6 myoblasts cultured with palmitic acid,the expression of PGC1 α,NRF1,UCP3,and COX1 were down compared with their expression in the NC group (P ＜ 0.05).However,the altered expression of PGC1α,NRF1,UCP3,and COX1 was reversed by transfecting with PGC1α-overexpression plasmids (F =30.079,96.883,226.772,respectively,P ＜ 0.001).Conclusions High-fat diets can lead to insulin resistance and decreased expression of mitochondrial energy metabolism-related genes,which can be reversed by PGC1α.The decreased expression of PGC1α may mediate the high-fat diet-induced mitochondrial dysfunction and IR.