A new combined multicompartmental model for apolipoprotein B-100 and triglyceride metabolism in VLDL subfractions

• The use of stable isotopes in conjunction with compartmental modeling analysis has greatly facilitated studies of the metabolism of the apolipoprotein B (apoB)-containing lipoproteins in humans. The aim of this study was to develop a multicompartment model that allows us to simultaneously determine the kinetics of apoB and triglyceride (TG) in VLDL(1) and VLDL(2) after a bolus injection of [(2)H(3)]leucine and [(2)H(5)]glycerol and to follow the catabolism and transfer of the lipoprotein particles. Here, we describe the model and present the results of its application in a fasting steady-state situation in 17 subjects with lipid values representative of a Western population. Analysis of the correlations showed that plasma TG was determined by the VLDL(1) and VLDL(2) apoB and TG fractional catabolic rate. Furthermore, the model showed a linear correlation between VLDL(1) TG and apoB production. A novel observation was that VLDL TG entered the circulation within 21 min after its synthesis, whereas VLDL apoB entered the circulation after 33 min. These observations are consistent with a sequential assembly model of VLDL and suggest that the TG is added to a primordial apoB-containing particle in the liver.

Nyckelord

Apolipoprotein B-100

Apolipoproteins B/biosynthesis/*metabolism

Deuterium/administration & dosage/metabolism

Glycerol/administration & dosage/metabolism

Humans

Kinetics

Leucine/administration & dosage/metabolism

Lipoproteins

VLDL/biosynthesis/*metabolism

Models

Biological

Protein Transport

Triglycerides/biosynthesis/*metabolism

Triglycerides/biosynthesis/*metabolism

Publikations- och innehållstyp

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