ABSTRACT
Monocarboxylate transporter (MCT)-1 mediates the transport of ketone bodies and other monocarboxylic acids across the plasma membrane. MCT1 is up-regulated by peroxisome proliferator-activated receptor (PPAR)-alpha, a transcription factor that mediates the adaptive response to fasting by up-regulation of genes involved in fatty acid oxidation and ketogenesis. Here, we show for the first time that MCT1 is up-regulated by dietary natural PPAR-alpha agonists. Both, an oxidized fat and conjugated linoleic acids increased MCT1 mRNA concentration in the liver of rats. Also, in the liver of pigs as non-proliferating species MCT1 was up-regulated upon PPAR-alpha activation by clofibrate, oxidized fat and fasting. Concomitant with up-regulation of MCT1, mRNA level of CD147 was increased in livers of rats and pigs. CD147 is a plasma membrane glycoprotein that is required for translocation and transport activity of MCT1. CD147 mRNA increase upon PPAR-alpha activation could not be observed in mice lacking PPAR-alpha, which also fail in up-regulation of MCT1 indicating a co-regulation of MCT1 and CD147. Analysis of the 5'-flanking region of mouse MCT1 gene by reporter gene assay revealed that promoter activity of mouse MCT1 was not induced by PPAR-alpha, indicating that the 5'-flanking region is not involved in MCT1 regulation by PPAR-alpha.
