Treatment with pharmacological peroxisome proliferator-activated receptor alpha agonist clofibrate increases intestinal carnitine absorption in rats.
Activation of PPARalpha by clofibrate has recently been shown to cause upregulation of the high-affinity carnitine transporter novel organic cation transporter (OCTN) 2 in small intestine. This strongly suggests that PPARalpha activation in response to clofibrate treatment improves the absorption of carnitine from the diet. To test this hypothesis, we performed an experiment with rats which were fed diets with or without 5 g clofibrate/kg diet and with or without 5 g L-carnitine/kg diet. PPARalpha was significantly activated by clofibrate in small intestine as evidenced by increased relative mRNA concentrations of the PPARalpha target gene acyl-CoA oxidase (P < 0.05). Relative mRNA concentration of OCTN2 in small intestine was significantly increased by clofibrate (P < 0.05) but not the carnitine supplementation, whereas relative mRNA concentrations of other carnitine transporters (OCTN1, ATB(0+)) in small intestine were not influenced by either clofibrate or carnitine. The absorption rate of carnitine in small intestine was markedly higher in rats treated with clofibrate than in those treated without clofibrate (P < 0.05). In conclusion, the present study shows that administration of clofibrate to rats increases carnitine absorption in small intestine which is probably due to the observed upregulation of OCTN2 mediated by activation of PPARalpha.
Ringseis
Robert
R
Institut für Agrar- und Ernährungswissenschaften, Martin-Luther-Universität Halle-Wittenberg, Emil-Abderhalden-Strasse 26, D-06108 Halle (Saale), Germany. robert.ringseis@landw.uni-halle.de
Lüdi
Silvia
S
Hirche
Frank
F
Eder
Klaus
K
D026905:Amino Acid Transport Systems / Q000096:biosynthesis; D000818:Animals; D002331:Carnitine / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis; D002994:Clofibrate / Q000494:pharmacology*; D004032:Diet; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects*; D007421:Intestine, Small / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D027701:Organic Cation Transport Proteins / Q000096:biosynthesis; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074058:Solute Carrier Family 22 Member 5; D000070590:Solute Carrier Proteins; D027981:Symporters
D026905:Amino Acid Transport Systems; D002352:Carrier Proteins; D000960:Hypolipidemic Agents; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; D047493:PPAR alpha; D012333:RNA, Messenger; C000705567:Slc22a4 protein, rat; C115441:Slc22a5 protein, rat; D000074058:Solute Carrier Family 22 Member 5; D000070590:Solute Carrier Proteins; D027981:Symporters; D002994:Clofibrate; D002331:Carnitine