Monocarboxylate transporter (MCT)-1 is up-regulated by PPARalpha.
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 PPARalpha in rats by clofibrate treatment or fasting increased hepatic mRNA concentration of MCT1. In Fao rat hepatoma cells, incubation with the PPARalpha agonist WY 14,643 increased mRNA concentration of MCT1 whereas the PPARgamma agonist troglitazone did not. To elucidate whether up-regulation of MCT1 is indeed mediated by PPARalpha we treated wild-type and PPARalpha-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 PPARalpha-null mice.
König
Bettina
B
Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, Halle, Germany. bettina.koenig@landw.uni-halle.de
Koch
Alexander
A
Giggel
Karen
K
Dordschbal
Batsuch
B
Eder
Klaus
K
Stangl
Gabriele I
GI
D000818:Animals; D002994:Clofibrate / Q000494:pharmacology; D005215:Fasting / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007657:Ketone Bodies / Q000378:metabolism*; D008297:Male; D051379:Mice; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009928:Organ Specificity / Q000187:drug effects / Q000502:physiology; D010084:Oxidation-Reduction / Q000187:drug effects; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism*; D020025:Peroxisome Proliferators / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D000099233:Monocarboxylate Transport Protein 1
D002994:Clofibrate; D005227:Fatty Acids; D000960:Hypolipidemic Agents; D007657:Ketone Bodies; D027501:Monocarboxylic Acid Transporters; D047493:PPAR alpha; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D012333:RNA, Messenger; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C006253:pirinixic acid