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Journal of Lipid Research, Vol. 43, 706-712, May 2002
Copyright © 2002 by Lipid Research, Inc.

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

Dick C. Chan^*, Gerald F. Watts^1,*, P. Hugh R. Barrett^*, Ian J. Martins, Anthony P. James, John C. L. Mamo, Trevor A. Mori^* and Trevor G. Redgrave

^* Departments of Medicine, University of Western Australia
Physiology, University of Western Australia
Department of Nutrition, Dietetics and Food Sciences, Curtin University of Technology, Western Australia

¹ To whom correspondence should be addressed at the University Department of Medicine, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847, Australia. e-mail: gfwatts{at}cyllene.uwa.edu.au

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 [¹³C]oleate was injected intravenously into patients; the fractional catabolic rate (FCR) of the remnant-like emulsion was determined by measurement of ¹³CO₂ 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-like 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 LDL-C (r = -0.575, P = 0.040), suggesting removal of LDL and chylomicron remnants by similar hepatic receptor pathways. We conclude that in obese subjects, inhibition of cholesterol synthesis with atorvastatin decreases the plasma concentrations of both LDL-C and triglyceride-rich remnants 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.

Abbreviations: apo, apolipoprotein; FCR, fractional catabolic rate; HOMA, homeostasis model assessment; RLP, remnant-like particle

Supplementary key words HMG-CoA reductase inhibitor • dyslipidaemia • triglyceride-rich lipoproteins

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