Induction of fatty acid synthesis by pravastatin sodium in rat liver and primary hepatocytes.
We examined the effect of pravastatin sodium (pravastatin), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on fatty acid synthesis in rat liver. The repeated administration of pravastatin 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 synthesis was not affected by the treatment. Hepatic fatty acid synthase activity was increased 3.2-fold, while acetyl-CoA carboxylase activity was not changed by the repeated administration of pravastatin. In rat hepatocytes, the incubation with 2 microg/ml pravastatin for 24 h increased fatty acid synthase activity 1.5-fold, as well as HMG-CoA reductase activity 2.8-fold. These results suggest that HMG-CoA reductase inhibitors might increase fatty acid synthesis in vivo through the induction of hepatic fatty acid synthase.
Fujioka
T
T
Pharmacology and Molecular Biology Research Laboratories, Sankyo Co., Ltd., Shinagawa-ku, Tokyo, Japan. fujiok@shina.sankyo.co.jp
Tsujita
Y
Y
Shimotsu
H
H
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D064429:Fatty Acid Synthases / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D017035:Pravastatin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019346:Sodium Acetate / Q000378:metabolism
D005227:Fatty Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019346:Sodium Acetate; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase; D017035:Pravastatin