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

被引:24
作者
Prinsen, BHCMT
Romijn, JA
Bisschop, PH
de Barse, MMJ
Barrett, PHR
Ackermans, M
Berger, R
Rabelink, TJ
de Sain-van der Velden, MGM [1 ]
机构
[1] Univ Utrecht, Ctr Med, Dept Metab Dis, Utrecht, Netherlands
[2] Univ Utrecht, Ctr Med, Dept Vasc Med & Metab, Utrecht, Netherlands
[3] Leiden Univ, Med Ctr, Dept Endocrinol, Leiden, Netherlands
[4] Univ Amsterdam, Acad Med Ctr, Dept Endocrinol & Metab, Amsterdam, Netherlands
[5] Univ Western Australia, Dept Med, Perth, WA, Australia
[6] Western Australia Inst Med Res, Perth, WA, Australia
关键词
apolipoprotein B-100; lathosterol; very low density lipoprotein;
D O I
10.1194/jlr.M300023-JLR200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (I-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 C-13-valine (15 mumol/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 I,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.
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页码:1341 / 1348
页数:8
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