ETOMOXIR, SODIUM 2-[6-(4-CHLOROPHENOXY)HEXYL]OXIRANE-2-CARBOXYLATE, INHIBITS TRIACYLGLYCEROL DEPLETION IN HEPATOCYTES AND LIPOLYSIS IN ADIPOCYTES

The effects of etomoxir, an inhibitor of mitochondrial long-chain fatt y acid oxidation, on triacylglycerol metabolism in rat hepatocytes and adipocytes were investigated. Etomoxir inhibited the depletion of tri acylglycerol stores in hepatocytes incubated without exogenous fatty a cids and inhibited lipolysis in adipocytes. The effects on hepatocytes could be attributed to two mechanisms. At low concentrations (1-10 mu M) R-etomoxir increased fatty acid esterification by inhibition of be ta-oxidation. This effect was specific for the R-enantiomer and was as sociated with increased triacylglycerol secretion. At higher concentra tions (50-100 mu M) RS-etomoxir inhibited lipolysis and triacylglycero l secretion, independently of inhibition of carnitine palmitoyltransfe rase I. These effects of RS-etomoxir on triacylglycerol metabolism and lipolysis may contribute to the chronic hypolipidaemic effects of eto moxir in vivo. (C) 1997 Federation of European Biochemical Societies.