Background: Recently, we have shown that activation of peroxisome proliferator-activated receptor (PPAR)-alpha by clofibrate leads to an upregulation of novel organic cation transporter (OCTN)-2, a carnitine transporter, and in turn increases the carnitine concentration in the liver of rats. In this study, we tested the hypothesis that fasting and caloric restriction, conditions under which PPARalpha activation also occurs, cause similar effects.
Methods: Three groups of rats received the diet either ad libitum (control rats) or 10.5 g diet/day (70% of energy requirement for maintenance, E70 rats) or 6 g diet/day (40% of energy requirement for maintenance, E40 rats) for 10 days. A 4th group received the diet ad libitum for 9 days and was then fasted for 24 h (fasted rats).
Results: Fasted and calorie-restricted rats had increased mRNA concentrations of acyl-CoA oxidase and carnitine palmitoyltransferase-1 in the liver, heart and kidneys compared to control rats (p < 0.05), indicative of activation of PPARalpha in these tissues. E70 rats had increased OCTN2 mRNA concentrations in liver (2.6-fold) and kidneys (1.5-fold) and increased total carnitine concentrations in these tissues compared to control rats. E40 rats had increased OCTN2 mRNA concentrations in the liver (3.3-fold), skeletal muscle (2.2-fold), heart (2.3-fold) and kidneys (3.5-fold) and increased total carnitine concentrations in these four tissues compared to control rats. Fasted rats had increased OCTN2 mRNA concentrations in the liver (4.0-fold), heart (2.1-fold) and kidneys (2.0-fold) and increased total carnitine concentrations in these three tissues (p < 0.05).
Conclusion: The study shows that fasting and caloric restriction lead to an upregulation of OCTN2 in several tissues, probably mediated by activation of PPARalpha. Increased tissue carnitine concentrations in fasted and calorie-restricted rats might be at least in part due to increased uptake of carnitine by OCTN2.
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