title: Endogenous cholesterol synthesis is associated with VLDL-2 apoB-100 production in healthy humans.
abstract: 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.
authors.affiliation: Department of Vascular Medicine and Metabolism, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Berthil H C M T
authors.initials: BH
authors.lastname: Prinsen
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.forename: Peter H
authors.initials: PH
authors.lastname: Bisschop
authors.forename: Martina M J
authors.initials: MM
authors.lastname: de Barse
authors.forename: P Hugh R
authors.initials: PH
authors.lastname: Barrett
authors.forename: Mariëtte
authors.initials: M
authors.lastname: Ackermans
authors.forename: Ruud
authors.initials: R
authors.lastname: Berger
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
authors.forename: Monique G M
authors.initials: MG
authors.lastname: de Sain-van der Velden
mesh_terms: 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
chemical_list: D000596:Amino Acids; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D015243:Cholesterol, VLDL; D007477:Ions; D008079:Lipoproteins, VLDL; C001521:lathosterol; D002784:Cholesterol; D014633:Valine