Spurway T D, Pogson C I, Sherratt H S, Agius L
Department of Medicine, University of Newcastle upon Tyne, UK.
FEBS Lett. 1997 Mar 3;404(1):111-4. doi: 10.1016/s0014-5793(97)00103-8.
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.
研究了线粒体长链脂肪酸氧化抑制剂依托莫西对大鼠肝细胞和脂肪细胞中三酰甘油代谢的影响。依托莫西抑制了在无外源脂肪酸情况下孵育的肝细胞中三酰甘油储备的消耗，并抑制了脂肪细胞中的脂肪分解。对肝细胞的影响可归因于两种机制。在低浓度（1 - 10微摩尔）时，R - 依托莫西通过抑制β - 氧化增加脂肪酸酯化。这种作用对R - 对映体具有特异性，并与三酰甘油分泌增加有关。在较高浓度（50 - 100微摩尔）时，RS - 依托莫西抑制脂肪分解和三酰甘油分泌，与肉碱棕榈酰转移酶I的抑制无关。RS - 依托莫西对三酰甘油代谢和脂肪分解的这些作用可能有助于依托莫西在体内的慢性降血脂作用。
