Treatment with pharmacological peroxisome proliferator-activated receptor alpha agonist clofibrate increases...

Activation of PPARalpha by clofibrate has recently been shown to cause upregulation of the high-affinity carnitine transporter novel organic cation transporter (OCTN) 2 in small intestine. This strongly suggests that PPARalpha activation in response to clofibrate treatment improves the absorption of carnitine from the diet. To test this hypothesis, we performed an experiment with rats which were fed diets with or without 5 g clofibrate/kg diet and with or without 5 g L-carnitine/kg diet. PPARalpha was significantly activated by clofibrate in small intestine as evidenced by increased relative mRNA concentrations of the PPARalpha target gene acyl-CoA oxidase (P < 0.05). Relative mRNA concentration of OCTN2 in small intestine was significantly increased by clofibrate (P < 0.05) but not the carnitine supplementation, whereas relative mRNA concentrations of other carnitine transporters (OCTN1, ATB(0+)) in small intestine were not influenced by either clofibrate or carnitine. The absorption rate of carnitine in small intestine was markedly higher in rats treated with clofibrate than in those treated without clofibrate (P < 0.05). In conclusion, the present study shows that administration of clofibrate to rats increases carnitine absorption in small intestine which is probably due to the observed upregulation of OCTN2 mediated by activation of PPARalpha.