PPARalpha agonists up-regulate organic cation transporters in rat liver cells.
It has been shown that clofibrate treatment increases the carnitine concentration in the liver of rats. However, the molecular mechanism is still unknown. In this study, we observed for the first time that treatment of rats with the peroxisome proliferator activated receptor (PPAR)-alpha agonist clofibrate increases hepatic mRNA concentrations of organic cation transporters (OCTNs)-1 and -2 which act as transporters of carnitine into the cell. In rat hepatoma (Fao) cells, treatment with WY-14,643 also increased the mRNA concentration of OCTN-2. mRNA concentrations of enzymes involved in carnitine biosynthesis were not altered by treatment with the PPARalpha agonists in livers of rats and in Fao cells. We conclude that PPARalpha agonists increase carnitine concentrations in livers of rats and cells by an increased uptake of carnitine into the cell but not by an increased carnitine biosynthesis.
Luci
Sebastian
S
Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, Emil-Abderhalden-Strasse 26, D-06108 Halle (Saale), Germany.
Geissler
Stefanie
S
König
Bettina
B
Koch
Alexander
A
Stangl
Gabriele I
GI
Hirche
Frank
F
Eder
Klaus
K
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D050482:Catecholamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002994:Clofibrate / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000378:metabolism*; D008297:Male; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D000075102:Organic Cation Transporter 2; D047493:PPAR alpha / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects
D050482:Catecholamine Plasma Membrane Transport Proteins; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; D047493:PPAR alpha; C493212:Slc22a1 protein, rat; C100590:Slc22a2 protein, rat; D002994:Clofibrate