Effect of peroxisome proliferator-activated receptors-α on improving insulin sensitivity and uncoupling proteins gene mRNA expression

OBJECTIVE To explore the effect of fenofibrate, a ligand of peroxisome proliferatpr-activated receptors-α(PPAR-α) ,on improving insulin sensitivity and uncoupling proteins(UCPs) gene mRNA expression in high fat-fed rat model with insulin resistance.METHODS Fenofibrate was administrated (100 mg·kg-1·d-1) for two weeks in high fat-fed rat model with insulin resistance. The insulin sensitivity was evaluated by hyperinsulinemic euglycomic clamp. The UCPs mRNA in liver and muscle were measured using RT-PCR.RESULTS Fenofibrate treatment reduced significantly the level of serum triglycerides(TG) and free fat acid(FFA), reduced body weight gain. It also increased glucose disposal rate, improved insulin sensitivity. Moreover, fenofibrate administration increased UCP-2 mRNA 62.8% in liver and increased UCP-3 mRNA 32.7% in muscle, whereas UCP-2 mRNA level in muscle did not changed significantly.CONCLUSION Fenofibrate reduced the level of serum TG and FFA, improved insulin sensitivity. The effect of improving sensitivity may involve in the overexpression of UCPs gene.