Monocarboxylate transporter (MCT)-1 is up-regulated by PPARα

Peroxisome proliferator-activated receptor (PPAR)-α mediates an adaptive response to fasting by up-regulation of genes involved in fatty acid oxidation and ketone body synthesis. Ketone bodies are transferred in and out of cells by monocarboxylate transporter (MCT)-1. In this study we observed for the first time that activation of PPARα in rats by clofibrate treatment or fasting increased hepatic mRNA concentration of MCT1. In Fao rat hepatoma cells, incubation with the PPARα agonist WY 14,643 increased mRNA concentration of MCT1 whereas the PPARγ agonist troglitazone did not. To elucidate whether up-regulation of MCT1 is indeed mediated by PPARα we treated wild-type and PPARα-null mice with WY 14,643. In wild-type mice, treatment with WY 14,643 increased mRNA concentrations of MCT1 in liver, kidney and small intestine whereas no up-regulation was observed in PPARα-null mice.