Dietary oxidised fat up regulates the expression of organic cation transporters in liver and small intestine and alters carnitine concentrations in liver, muscle and plasma of rats

Abstract

It has been shown that treatment of rats with clofibrate, a synthetic agonist of PPARalpha, increases mRNA concentration of organic cation transporters (OCTN)-1 and -2 and concentration of carnitine in the liver. Since oxidised fats have been demonstrated in rats to activate hepatic PPARalpha, we tested the hypothesis that they also up regulate OCTN. Eighteen rats were orally administered either sunflower-seed oil (control group) or an oxidised fat prepared by heating sunflower-seed oil, for 6 d. Rats administered the oxidised fat had higher mRNA concentrations of typical PPARalpha target genes such as acyl-CoA oxidase, cytochrome P450 4A1 and carnitine palmitoyltransferases-1A and -2 in liver and small intestine than control rats (P < 0.05). Furthermore, rats treated with oxidised fat had higher hepatic mRNA concentrations of OCTN1 (1.5-fold) and OCTN2 (3.1-fold), a higher carnitine concentration in the liver and lower carnitine concentrations in plasma, gastrocnemius and heart muscle than control rats (P < 0.05). Moreover, rats administered oxidised fat had a higher mRNA concentration of OCTN2 in small intestine (2.4-fold; P < 0.05) than control rats. In conclusion, the present study shows that an oxidised fat causes an up regulation of OCTN in the liver and small intestine. An increased hepatic carnitine concentration in rats treated with the oxidised fat is probably at least in part due to an increased uptake of carnitine into the liver which in turn leads to reduced plasma and muscle carnitine concentrations. The present study supports the hypothesis that nutrients acting as PPARalpha agonists influence whole-body carnitine homeostasis.