INDUCTION OF FATTY-ACID SYNTHESIS BY PRAVASTATIN SODIUM IN RAT-LIVER AND PRIMARY HEPATOCYTES

We examined the effect of pravastatin sodium (pravastatin), a 3-hydrox y-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on fatty acid synthesis in rat liver. The repeated administration of pravastati n to rats at 250 mg/kg for 7 days led to a 2.8-fold increase in fatty acid synthesis in the liver. The diurnal change of fatty acid synthesi s was not affected by the treatment. Hepatic fatty acid synthase activ ity was increased 3.2-fold, while acetyl-CoA carboxylase activity was not changed by the repeated administration of pravastatin. In rat hepa tocytes, the incubation with 2 mu g/ml pravastatin for 24 h increased fatty acid synthase activity 1.5-fold, as well as HMG-CoA reductase ac tivity 2.8-fold. These results suggest that HMG-CoA reductase inhibito rs might increase fatty acid synthesis in vivo through the induction o f hepatic fatty acid synthase. (C) 1997 Elsevier Science B.V.