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.