Effect of simvastatin (MK-733) on plasma triacylglycerol levels in rats.
The effect of simvastatin (MK-733), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on plasma triacylglycerol (TG) levels was studied in rats. Dietary administration of MK-733 (0.055%, w/w) for 7 days significantly (P less than 0.05) reduced plasma TG levels by 30.6% associated with a 44.3% significant (P less than 0.01) reduction in very low density lipoprotein TG (VLDL-TG) as compared to those in the concurrent control rats. Clofibrate (0.08%, w/w) also significantly (P less than 0.05) decreased plasma TG levels by 26.1%. MK-733 did not affect the triacylglycerol secretion rate (TGSR) during 0-1.5 hr after administration of Triton WR-1339, but reduced it by 33.9% during 1.5-3.0 hr. Clofibrate also decreased TGSR during 1.5-3.0 hr. MK-733 increased lipoprotein lipase (LPL) activity in epididymal adipose tissue and thigh muscle by 36.3 and 55.0% respectively. MK-733 significantly (P less than 0.05) increased LPL activity in the post-heparin plasma by 21.5%, although it did not affect hepatic triacylglycerol lipase (H-TGL) activity. Clofibrate did not affect LPL activity in the tissues or LPL and H-TGL activities in the post-heparin plasma. It is considered that the mechanism of plasma TG-lowering effect of MK-733 is the removal of VLDL-TG by an increase in LPL activity in the tissues as well as a decrease in the TGSR.
Sato
A
A
Central Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Watanabe
K
K
Fukuzumi
H
H
Hase
K
K
Ishida
F
F
Kamei
T
T
D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002994:Clofibrate / Q000494:pharmacology; D002149:Energy Intake; D008071:Lipoprotein Lipase / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009132:Muscles / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D019821:Simvastatin; D014280:Triglycerides / Q000097:blood*
D008074:Lipoproteins; D014280:Triglycerides; D008148:Lovastatin; D019821:Simvastatin; D008071:Lipoprotein Lipase; D002994:Clofibrate