Effects of fenofibrate on gene expression of carnitine palmitoyltransferase 1 in liver and skeletal muscle and its influence on insulin sensitivity

Abstract

To study the effects of fenofibrate (FF), a peroxisome proliferator activated receptor (PPAR) alpha activator, on the expression of carnitine palmitoyltransferase 1 (CPT-1) mRNA in liver and muscle and its influence on insulin sensitivity. Thirty-two normal 8 week-old male SD rats were randomly divided into 3 groups: normal control group, fed with normal food for 3 weeks (NC group, n = 10), high fat diet group, fed with high fat food (HF group, n = 10), and high fat diet supplemented with FF group, fed with high fat food and given with gastric perfusion of FF (50 mg x kg(-1) x d(-1)) (FF group, n = 12). Fast serum triglyceride (TG) level was tested by automatic biochemical analyzer after 8-10 h fasting. Euglycemic-hyperinsulinemic clamp method was used to calculate the glucose infusion rate (GIR) so as to evaluate the insulin sensitivity. By the end of experiment the rats were killed with their internal organs taken out. The triglyceride (TG) contents of liver and skeletal muscle were measured using Folch method. Real-time PCR was used to detect the mRNA expression. of CPT-1 in the liver and skeletal muscles. As compared with the NC group, the TG levels of serum, liver, and skeletal muscle of the HF group were higher than those of the NC group by 0.45-fold, 2.14-fold, and 10.64-fold respectively. The GIR of the HF group was (6.2 +/- 0.8) mg x kg(-1) x min(-1), significantly lower than that of the NC group (15.8 +/- 2.1) mg x kg(-1) x min(-1), (P < 0.01), and that of the P < 0.01. The CPT-1 mRNA expression in liver of the HF group was not significantly different from that of the NC group (P > 0.05); the expression of CPT-1 mRNA in skeletal muscle of the HF group was lower than that of the NC group by 71% (P < 0.01). The CPT-1 mRNA expression in liver and skeletal muscle of the FF group were significantly higher than those of the HF group by 1.00 and 1.05 times respectively (both P < 05). The GIR was negatively correlated with the levels in the liver (r = -0.87, P < 0.01) and in the skeletal muscle (r = -0.78, P < 0.01). Fenofibrate promotes the oxygenation of fatty acids by up-regulating the CPT-1 mRNA expression in the liver and skeletal muscles, thus improving the insulin sensitivity.