Abstract
Rat hepatocyte cultures have higher rates of β-oxidation of palmitate and lower rates of esterification to glycerolipid than human or guinea pig hepatocytes. The R-enantiomer of etomoxir (sodium 2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate), a hypoglycaemic compound and inhibitor of carnitine palmitoyltransferase I, inhibited palmitate β-oxidation in all three species, but the sensitivity to inhibition was highest in human hepatocytes and lowest in rat hepatocytes. The concentration causing half-maximal inhibition was approximately: 0.1 μM in human; 1 μM in guinea pig and 10 μM in rat hepatocytes. In human and in guinea pig hepatocytes the inhibition of β-oxidation by R-etomoxir was associated with an increase in the esterification of palmitate but in rat hepatocytes R-etomoxir lowered the total rate of palmitate metabolism. The S-enantiomer of etomoxir had no significant effect on β-oxidation or esterification of palmitate in any of the three species. It is concluded that there are significant differences between human, rat and guinea pig hepatocytes, not only in the relative partitioning of palmitate between β-oxidation and esterification, but also in the sensitivity to an inhibitor of carnitine palmitoyltransferase I.
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