Monocarboxylate transporter 1 and CD147 are up-regulated by natural and synthetic peroxisome proliferator-activated receptor alpha agonists in livers of rodents and pigs

Mol Nutr Food Res. 2010 Sep;54(9):1248-56. doi: 10.1002/mnfr.200900432.


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.

MeSH terms

  • Animals
  • Basigin / genetics
  • Basigin / metabolism*
  • Dietary Fats / administration & dosage*
  • Female
  • Hydroxymethylglutaryl-CoA Synthase / genetics
  • Hydroxymethylglutaryl-CoA Synthase / metabolism
  • Linoleic Acids, Conjugated / administration & dosage
  • Lipid Peroxides / administration & dosage
  • Lipid Peroxides / analysis
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, 129 Strain
  • Mice, Knockout
  • Monocarboxylic Acid Transporters / genetics
  • Monocarboxylic Acid Transporters / metabolism*
  • PPAR alpha / agonists*
  • PPAR alpha / genetics
  • PPAR alpha / physiology
  • Promoter Regions, Genetic / drug effects
  • RNA, Messenger / metabolism
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Sus scrofa
  • Symporters / genetics
  • Symporters / metabolism*
  • Up-Regulation* / drug effects


  • Dietary Fats
  • Linoleic Acids, Conjugated
  • Lipid Peroxides
  • Monocarboxylic Acid Transporters
  • PPAR alpha
  • RNA, Messenger
  • Symporters
  • monocarboxylate transport protein 1
  • Basigin
  • Hydroxymethylglutaryl-CoA Synthase