Objective: To observe the effects of fenofibrate on the expression of peroxisome proliferator-activated (PPAR)-gamma coactivator-1α (PGC-1α) in skeletal muscle of rats with insulin resistance (IR) induced by elevated plasma free fatty acid (FFA) levels.
Methods: Male Sprague-Dawley (SD) rats were randomly divided into three groups: control group (Con, infused with saline), lipid infusion group (FFA) and fenofibrate treatment plus lipid infusion group (F-FFA). Plasma glucose, insulin and FFA were measured. Glucose infusion rate (GIR) was used to evaluate the insulin sensitivity by euglycemic-hyperinsulinemic clamp. The gene expression of PGC-1α in skeletal muscle was determined by real-time polymerase chain reaction (PCR).
Results: Compared with the control group, the levels of plasma FFA and insulin were elevated significantly in rats infused with lipid, but they decreased significantly in rats pretreated with fenofibrate then infused with lipid [FFA, Con: 0.46 (0.08 - 0.72) mmol/L, FFA: 1.45(0.87-1.70) mmol/L, F-FFA: 0.54 (0.06 - 0.84) mmol/L, all P < 0.01; Insulin, Con: (6.56 ± 0.78) µIU/ml, FFA: (10.54 ± 0.86) µIU/ml, F-FFA: (6.69 ± 0.84) µIU/ml, all P < 0.01]. In addition, the plasma glucose levels did not change markedly after lipid infusion; GIR was significantly reduced by 55.6% in lipid infusion group, but fenofibrate-pretreatment increased glucose infusion rate (GIR) [Con: (25.13 ± 2.10) mg×kg(-1)×min(-1), FFA: (10.16 ± 0.75) mg×kg(-1)×min(-1), F-FFA: (21.72 ± 2.89) mg×kg(-1)×min(-1), all P < 0.01]; the mRNA expression of PGC-1α decreased by about 71% in lipid infusion group but fenofibrate increased the gene expression by about 150% as compared with FFA group (all P < 0.01).
Conclusion: The elevation of plasma FFA levels may induce IR, and it also decreases the mRNA expression of PGC-1α in skeletal muscle. And fenofibrate pretreatment reverses these changes.
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