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

Peroxisome proliferator-activated receptor (PPAR)-alpha 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 PPAR alpha in rats by clofibrate treatment or fasting increased hepatic mRNA concentration of MCT1 In Fao rat hepatoma cells, incubation with the PPAR alpha agonist WY 14,643 increased mRNA concentration of MCT1 whereas the PPAR gamma agonist troglitazone did not. To elucidate whether up-regulation of MCT1 is indeed mediated by PPAR alpha we treated wild-type and PPAR alpha-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 PPAR alpha-null mice. (c) 2008 Elsevier B.V. All rights reserved.