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 fatty acid oxidation, on triacylglycerol metabolism in rat hepatocytes and adipocytes were investigated. Etomoxir inhibited the depletion of triacylglycerol stores in hepatocytes incubated without exogenous fatty acids and inhibited lipolysis in adipocytes. The effects on hepatocytes could be attributed to two mechanisms. At low concentrations (1-10 microM) R-etomoxir increased fatty acid esterification by inhibition of beta-oxidation. This effect was specific for the R-enantiomer and was associated with increased triacylglycerol secretion. At higher concentrations (50-100 microM) RS-etomoxir inhibited lipolysis and triacylglycerol secretion, independently of inhibition of carnitine palmitoyl-transferase I. These effects of RS-etomoxir on triacylglycerol metabolism and lipolysis may contribute to the chronic hypolipidaemic effects of etomoxir in vivo.
Spurway
T D
TD
Department of Medicine, University of Newcastle upon Tyne, UK.
Pogson
C I
CI
Sherratt
H S
HS
Agius
L
L
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004852:Epoxy Compounds / Q000494:pharmacology*; D004951:Esterification / Q000187:drug effects; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism*
D004852:Epoxy Compounds; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D014280:Triglycerides; C054207:etomoxir