3-hydroxy-3-methylglutaryl CoA reductase inhibitors reduce serum triglyceride levels through modulation of apolipoprotein C-III and lipoprotein lipase

Statins are hypolipidemic drugs which not only improve cholesterol but also triglyceride levels, Whereas their cholesterol-reducing effect involves in hibition of de novo biosynthesis of cellular cholesterol through competitiv e inhibition of its rate-limiting enzyme 3-hydroxy-3-methylglutaryl CoA red uctase, the mechanism by which they lower triglycerides remains unknown and forms the subject of the current study, Treatment of normal rats for 4 day s with simvastatin decreased serum triglycerides significantly, whereas it increased high density lipoprotein cholesterol moderately. The decrease in triglyceride concentrations after simvastatin was caused by a reduction in the amount of very low density lipoprotein particles which mere of an uncha nged lipid composition. Simvastatin administration increased the lipoprotei n lipase mRNA and activity in adipose tissue and heart. This effect on lipo protein lipase was accompanied by decreased mRNA as well as plasma levels o f the lipoprotein lipase inhibitor apolipoprotein C-III. These results sugg est that the triglyceride-lowering effect of statins involves a stimulation of lipoprotein lipase-mediated clearance of triglyceride-rich lipoproteins . (C) 1999 Federation of European Biochemical Societies.