Effects of atorvastatin and n−3 fatty acid supplementation on VLDL apolipoprotein C-III kinetics in men with abdominal obesity

Abstract

Disturbed apolipoprotein (apo) C-III metabolism in obese subjects may account for hypertriglyceridemia and increased risk of cardiovascular disease. Atorvastatin and fish oils decrease plasma triglycerides and VLDL concentrations, but the underlying mechanisms are not fully understood. We studied the independent and combined effects of atorvastatin and fish oils on the metabolism of VLDL apo C-III in obese men. We carried out a 6-wk randomized, placebo-controlled, 2 x 2 factorial intervention study of atorvastatin (40 mg/d) and fish oils (4 g/d) on VLDL apo C-III kinetics in the postabsorptive state in 39 abdominally obese men using intravenous administration of d(3)-leucine. VLDL apo C-III isotopic enrichments were measured by using gas chromatography-mass spectrometry with kinetic parameters derived by using a multicompartmental model. Atorvastatin significantly (P < 0.05, main effect) increased the VLDL apo C-III fractional catabolic rate (+0.06 +/- 0.003 pools/d) without significantly altering its production rate (-0.14 +/- 0.18 mg . kg(-1) . d(-1)), accounting for a significant reduction in plasma VLDL apo C-III pool size (-44 +/- 17 mg/L). Fish-oil supplementation significantly decreased plasma triglycerides but did not significantly alter plasma VLDL apo C-III concentrations or kinetic parameters. Combination treatment provided no additional effect on VLDL apo C-III concentrations or kinetics compared with atorvastatin alone. In obesity, the triglyceride-lowering effect of atorvastatin, but not fish oils, is associated with increased VLDL apo C-III fractional catabolism and hence lower VLDL apo C-III concentrations. Combination treatment provided no significant additional improvement in VLDL apo C-III metabolism compared with atorvastatin alone.