Effects of lovastatin on hepatic fatty acid metabolism

Lipids - Tập 28 Số 12 - Trang 1087-1093 - 1993
Manuel Guzmán1, José Emilio Cortés1, José María Albertos Castro1
1Department of Biochemistry and Molecular Biology I, Faculty of Chemistry, Complutense University, Madrid, Spain

Tóm tắt

AbstractThein vitro andin vivo effects of lovastatin on fatty acid metabolism were studied in isolated rat hepatocytes. When addedin vitro to cell incubations, lovastatin stimulatedde novo fatty acid synthesis and acetyl‐CoA carboxylase activity, whereas fatty acid synthase, activity was unaffected. Lovastatin depressed palmitate, but not octanoate, oxidation. This may be attributed to the lovastatin‐induced increase, in intracellular malonyl‐CoA levels, as no concomitant changes of carnitine palmitoyltransferase I (CPT‐I) specific activity was detected. Lovastatin had no effect on the synthesis and secretion of triacylglycerols and phospholipids in the form of very low density lipoproteins (VLDL). When rats were fed a diet supplemented with 0.1% (w/w) lovastatin for one week, both acetyl‐CoA carboxylase activity andde novo fatty acid synthesis were reduced compared to pair‐fed controls, whereas fatty acid synthase activity was unaffected. Palmitate oxidation was enhanced in the lovastatin‐fed group. There was an increase in CPT‐I activity but no change in intracellular concentration of malonyl‐CoA. Lovastatin feeding and no significant effect either on the esterification of exogenous palmitic acid into both cellular and VLDL triacylglycerols and phospholipids or on hepatic lipid accumulation. Thein vitro andin vivo effects of lovastatin were not significantly different between periportal and perivenous hepatocytes. The results indicate that: (i) the administration of lovastatin increased the fatty acid‐oxidative capacity of the liver at the expense of its lipogenic capacity, (ii) the rate ofde novo cholesterol synthesis did not seem to be a limiting factor in the synthesis and secretion of VLDL and (iii) lovastatin produced opposite effects on hepatic fatty acid metabolismin vitro andin vivo.

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Lipids

Tập 28 Số 12

1087-1093

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