Monocarboxylate transporter 1 and CD147 are up-regulated by natural and synthetic peroxisome proliferator-activated receptor α agonists in livers of rodents and pigs
✍ Scribed by Bettina König; Susanne Fischer; Susanne Schlotte; Gaiping Wen; Klaus Eder; Gabriele I. Stangl
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 209 KB
- Volume
- 54
- Category
- Article
- ISSN
- 1613-4125
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✦ Synopsis
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)‐α, 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‐α 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‐α 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‐α activation could not be observed in mice lacking PPAR‐α, 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‐α, indicating that the 5′‐flanking region is not involved in MCT1 regulation by PPAR‐α.