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Published on: March 28, 2013
Monocarboxylate transporter (MCT)-1 is up-regulated by PPARalpha
Bettina König1, Alexander Koch, Karen Giggel
1Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, Halle, Germany. bettina.koenig@landw.uni-halle.de
Peroxisome proliferator-activated receptor (PPAR)-alpha activation increases monocarboxylate transporter (MCT)-1 mRNA levels. This study demonstrates PPAR-alpha
Area of Science:
- Metabolism
- Molecular Biology
- Cell Biology
Background:
- Peroxisome proliferator-activated receptor (PPAR)-alpha regulates adaptive responses to fasting, including fatty acid oxidation and ketone body synthesis.
- Monocarboxylate transporter (MCT)-1 facilitates cellular transport of ketone bodies.
Purpose of the Study:
- To investigate the role of PPAR-alpha in regulating MCT1 expression.
- To determine if PPAR-alpha activation leads to increased MCT1 mRNA levels.
Main Methods:
- Treatment of rats with clofibrate or fasting to activate PPAR-alpha.
- Incubation of Fao rat hepatoma cells with PPAR-alpha and PPAR-gamma agonists.
- Administration of a PPAR-alpha agonist (WY 14,643) to wild-type and PPAR-alpha-null mice.
Main Results:
- PPAR-alpha activation by clofibrate or fasting increased hepatic MCT1 mRNA in rats.
- WY 14,643 increased MCT1 mRNA in Fao cells, while troglitazone (PPAR-gamma agonist) did not.
- WY 14,643 treatment elevated MCT1 mRNA in the liver, kidney, and small intestine of wild-type mice, but not in PPAR-alpha-null mice.
Conclusions:
- PPAR-alpha activation up-regulates MCT1 mRNA expression.
- The up-regulation of MCT1 by PPAR-alpha agonists is mediated through PPAR-alpha.
- These findings highlight a novel role for PPAR-alpha in regulating ketone body transport.
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