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 obesity. We examined the effect of atorvastatin on chylomicron remnant metabolism in 25 obese men with dyslipidaemia. A remnant-like emulsion labeled with cholesteryl [C-13]oleate was injected intravenously into patients; the fractional catabolic rate (FCR) of the remnant-like emulsion was determined by measurement of (CO2)-C-13 in the breath and analyzed using compartmental modelling. Compared with placebo, atorvastatin significantly decreased the plasma concentrations of total cholesterol, triglycerides, LDL cholesterol, apolipoprotein B (apoB), and lathosterol (P <0.001). ApoB-48 and remnant-ne particle-cholesterol (RLP-C) both decreased 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 LDLC (r = -0.575, P = 0.040), suggesting removal of LDL and chylomicron remnants by similar hepatic receptor pathway. We conclude diet in obese Subjects, inhibition of cholesterol synthesis with atorvastatin decreases the plasma concentrations of both LDLC and triglyceride-rich remnants and that this may be partially due to an enhancement in hepatic clearance of these lipoproteins.