Abstract
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.
Highlights
The use of stable isotopes in conjunction with compartmental modeling analysis has greatly facilitated studies of the metabolism of the apolipoprotein B-containing lipoproteins in humans
To enhance our understanding of the pathways leading to VLDL1 and VLDL2 and of the metabolic fate of these particles, we developed for the first time a multicompartmental mathematical model that allows the kinetics of TG and apolipoprotein B (apoB)-100 in VLDL1 and VLDL2 to be simultaneously assessed after a bolus injection of glycerol and leucine
TG was removed from VLDL1 by three pathways: particles transferred from VLDL1 to VLDL2, particles removed by direct catabolism (i.e., VLDL1 particle uptake by cells), and TG removal by hydrolysis
Summary
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 VLDL1 and VLDL2 after a bolus injection of [2H3]leucine and [2H5]glycerol and to follow the catabolism and transfer of the lipoprotein particles. Multicompartmental modeling improves the accuracy by attempting to account for tracer recycling [3,4,5,6,7,8] Such studies have revealed that VLDL1 apolipoprotein B-100 (apoB-100) production and VLDL2 apoB-100 production are independently regulated [9,10,11], indicating that regulatory steps in the assembly of VLDL govern the lipid content of the secreted particles. The model and present the results of its application in 17 subjects with lipid values representative of a Western population
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