Effect of atorvastatin on chylomicron remnant metabolism in visceral obesity: a study employing a new stable isotope breath test

Elevated plasma concentration of chylomicron remnants may be causally related to atherosclerosis in obe- sity. We examined the effect of atorvastatin on chylomicron remnant metabolism in 25 obese men with dyslipidaemia. A remnant-like emulsion labeled with cholesteryl ( 13 C)oleate was injected intravenously into patients; the fractional cata- bolic rate (FCR) of the remnant-like emulsion was deter- mined by measurement of 13 CO 2 in the breath and analyzed using compartmental modelling. Compared with placebo, atorvastatin significantly decreased the plasma concentra- tions of total cholesterol, triglycerides, LDL cholesterol, apolipoprotein B (apoB), and lathosterol ( P � 0.001). ApoB- 48 and remnant-like particle-cholesterol (RLP-C) both de- creased significantly by 23% ( P � 0.002) and 33% ( P � 0.045), respectively. The FCR of the remnant-like emulsion increased significantly from 0.054 � 0.008 to 0.090 � 0.010 pools/h ( P � 0.002). The decrease in RLP-C was associated with the decrease in plasma triglycerides ( r � 0.750, P � 0.003). Furthermore, the change in FCR of remnant-like emulsions was inversely associated with the change in LDL-C ( r � � 0.575, P � 0.040), suggesting removal of LDL and chylomicron remnants by similar hepatic receptor path- ways. We conclude that in obese subjects, inhibition of cholesterol synthesis with atorvastatin decreases the plasma concentrations of both LDL-C and triglyceride-rich rem- nants and that this may be partially due to an enhancement in hepatic clearance of these lipoproteins. —Chan, D. C., G. F. Watts, P. H. R. Barrett, I. J. Martins, A. P. James, J. C. L. Mamo, T. A. Mori, and T. G. Redgrave. Effect of atorvastatin on chylomicron remnant metabolism in visceral obesity: a study employing a new stable isotope breath test. J. Lipid Res. 2002. 43: 706-712.