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Journal of Lipid Research, Vol. 44, 1341-1348, July 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

Endogenous cholesterol synthesis is associated with VLDL-2 apoB-100 production in healthy humans

Berthil H. C. M. T. Prinsen^*,, Johannes A. Romijn, Peter H. Bisschop^**, Martina M. J. de Barse, P. Hugh R. Barrett, Mariëtte Ackermans^**, Ruud Berger, Ton J. Rabelink and Monique G. M. de Sain-van der Velden^1,

^* Department of Vascular Medicine and Metabolism, University Medical Center Utrecht, Utrecht, The Netherlands
Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands
Department of Endocrinology, Leiden, University Medical Center, The Netherlands
^** Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands
Department of Medicine, University of Western Australia and the Western Australia Institute for Medical Research, Perth, Australia

¹ To whom correspondence should be addressed. e-mail: m.g.desain{at}lab.azu.nl

Subjects with high plasma cholesterol levels exhibit a high production of VLDL apolipoprotein B-100 (apoB-100), suggesting that cholesterol is a mediator for VLDL production. The objective of the study was to examine whether endogenous cholesterol synthesis, reflected by the lathosterol-cholesterol ratio (L-C ratio), affects the secretory rates of different VLDL subfractions. Ten healthy subjects were studied after overnight fasting. During a 10 h primed, constant infusion of ¹³C-valine (15 µmol/kg/h), enrichment was determined in apoB-100 from ultracentrifugally isolated VLDL-1 and VLDL-2 by gas chromatography mass spectrometry. The synthesis rates of VLDL-1 apoB-100 and VLDL-2 apoB-100, catabolism, and transfer were estimated by compartmental analysis. Mean VLDL-1 apoB-100 pool size was 90 ± 15 mg, and mean VLDL-2 apoB-100 pool size was 111 ± 14 mg. Absolute synthesis rate of VLDL-1 apoB-100 was 649 ± 127 mg/day and 353 ± 59 mg/day for VLDL-2 apoB-100. There was a strong association between the absolute synthesis rate of VLDL-2 apoB-100 and L-C ratio (r ² = 0.61, P < 0.01). In contrast, no correlation was observed between L-C ratio and absolute synthesis rate of VLDL-1 apoB-100 (r ² = 0.302, P = 0.09). In conclusion, these data provide additional support for an independent regulation of VLDL-1 apoB-100 and VLDL-2 apoB-100 production.

Endogenous cholesterol synthesis is correlated only with the VLDL-2 apoB-100 production.

Supplementary key words apolipoprotein B-100 • lathosterol • very low density lipoprotein

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