Endogenous cholesterol synthesis is associated with VLDL-2 apoB-100 production in healthy humans.
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 micromol/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.
Prinsen
Berthil H C M T
BH
Department of Vascular Medicine and Metabolism, University Medical Center Utrecht, Utrecht, The Netherlands.
Romijn
Johannes A
JA
Bisschop
Peter H
PH
de Barse
Martina M J
MM
Barrett
P Hugh R
PH
Ackermans
Mariëtte
M
Berger
Ruud
R
Rabelink
Ton J
TJ
de Sain-van der Velden
Monique G M
MG
D000328:Adult; D000596:Amino Acids / Q000737:chemistry; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000096:biosynthesis* / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D015243:Cholesterol, VLDL / Q000378:metabolism; D005260:Female; D006801:Humans; D007477:Ions; D007700:Kinetics; D008079:Lipoproteins, VLDL / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D013997:Time Factors; D014633:Valine / Q000737:chemistry
D000596:Amino Acids; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D015243:Cholesterol, VLDL; D007477:Ions; D008079:Lipoproteins, VLDL; C001521:lathosterol; D002784:Cholesterol; D014633:Valine