Clofibrate treatment up-regulates novel organic cation transporter (OCTN)-2 in tissues of pigs as a model of non-proliferating species.
Recent studies have shown that treatment of rodents with agonists of peroxisome proliferator-activated receptor (PPAR)-alpha causes an up-regulation of novel organic cation transporter (OCTN)-2, a carnitine transporter, and increases carnitine concentration in the liver. This study was performed to investigate whether such effects occur also in pigs which like humans have a lower expression of PPAR alpha and are less responsive to treatment with PPAR alpha agonists than rodents. An experiment with 18 pigs was performed which were fed a control diet or the same diet supplemented with 5 g clofibrate/kg for 28 days. Pigs treated with clofibrate had higher relative mRNA concentrations of OCTN2 in liver (3.1-fold), skeletal muscle (1.5-fold) and epithelial cells from small intestine (1.8-fold) than control pigs (P<0.05). Pigs treated with clofibrate had also higher concentrations of free and total carnitine in the liver and a higher concentration of free carnitine in skeletal muscle than control pigs (P<0.05). Concentrations of gamma-butyrobetaine, the precursor of endogenous formation of carnitine, in liver, muscle and plasma did not differ between both groups; the activity of gamma-butyrobetaine dioxygenase, the rate limiting enzyme of carnitine synthesis, in the liver was lower in pigs treated with clofibrate than in control pigs (P<0.05). This study shows for the first time that treatment with a PPAR alpha agonist causes an up-regulation of OCTN2 in liver, muscle and enterocytes from small intestine of pigs. This in turn increases carnitine concentrations in liver and muscle probably by enhancing carnitine uptake into cells.
Ringseis
Robert
R
Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, Emil-Abderhalden-Strasse 26, D-06108 Halle (Saale), Germany.
Luci
Sebastian
S
Spielmann
Julia
J
Kluge
Holger
H
Fischer
Maren
M
Geissler
Stefanie
S
Wen
Gaiping
G
Hirche
Frank
F
Eder
Klaus
K
D000818:Animals; D001622:Betaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D001835:Body Weight / Q000187:drug effects; D002331:Carnitine / Q000096:biosynthesis / Q000378:metabolism / Q000493:pharmacokinetics; D002994:Clofibrate / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D027701:Organic Cation Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D047493:PPAR alpha / Q000819:agonists; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D014018:Tissue Distribution; D015854:Up-Regulation / Q000187:drug effects; D050563:gamma-Butyrobetaine Dioxygenase / Q000378:metabolism
D000960:Hypolipidemic Agents; D027701:Organic Cation Transport Proteins; D047493:PPAR alpha; D012333:RNA, Messenger; D001622:Betaine; C002889:gamma-butyrobetaine; D012313:RNA; D050563:gamma-Butyrobetaine Dioxygenase; D002994:Clofibrate; D002331:Carnitine