Mechanism of Action of a 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor on Apolipoprotein B-100 Kinetics in Visceral Obesity

Publisher Website
Google Scholar
Abstract
We examined the effect of atorvastatin, an inhibitor of 3- hydroxy-3-methylglutaryl coenzyme A reductase, on the kinetics of apolipoprotein B-100 (apoB) metabolism in 25 viscerally obese men in a placebo-controlled study. Very- low-density lipoprotein (VLDL), intermediate-density lipo- protein (IDL), and low-density lipoprotein (LDL) apoB kinetics were measured using an iv bolus injection of (2H3)- leucine. ApoB isotopic enrichment was measured using gas chromatography-mass spectrometry. Kinetic parameters were derived by using a multicompartmental model (SAAM- II). Compared with the placebo group, atorvastatin treat- ment resulted in significant (P < 0.001) decreases in total cholesterol (34%), triglyceride (19%), LDL cholesterol (42%), total apoB (39%), and lathosterol (86%); VLDL- apoB, IDL-apoB, and LDL-apoB pool sizes also fell signifi- cantly (P < 0.002) by 27%, 22%, and 41%, respectively. This was associated with an increase in the fractional catabolic rates of VLDL-apoB (58%, P 0.019), IDL-apoB (40%, P 0.049), and LDL-apoB (111%, P 0.001). How- ever, atorvastatin did not significantly alter the production and conversion rates of apoB in all lipoproteins. We con- clude that in obese subjects, atorvastatin decreases the plasma concentration of all apoB-containing lipoproteins chiefly by increasing their catabolism and not by decreas- ing their production or secretion. This may be owing to up-regulation of hepatic receptors as a consequence of inhibition of cholesterogenesis. (J Clin Endocrinol Metab 87: 2283-2289, 2002)

This publication has 0 references indexed in Scilit: