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Effects of lovastatin on hepatic fatty acid metabolism
Author(s) -
Guzmán Manuel,
Cortés Josefa P.,
Castro José
Publication year - 1993
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02537075
Subject(s) - lovastatin , fatty acid , carnitine palmitoyltransferase i , biochemistry , carnitine , palmitic acid , coenzyme a , biology , malonyl coa , metabolism , fatty acid synthase , fatty acid synthesis , lipid metabolism , beta oxidation , fatty acid metabolism , acetyl coa carboxylase , chemistry , endocrinology , pyruvate carboxylase , cholesterol , enzyme , reductase
The in vitro and in vivo effects of lovastatin on fatty acid metabolism were studied in isolated rat hepatocytes. When added in vitro to cell incubations, lovastatin stimulated de 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 and de 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. The in vitro and in 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 of de 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 metabolism in vitro and in vivo .