Development and application of a multicompartmental model to study very low density lipoprotein subfraction metabolism

Abstract

A multicompartmental model has been devised to explain apolipoprotein B (apoB) kinetics in very low density lipoprotein subfractions (VLDL1 Sf 60-400 and VLDL2 Sf 20-60), intermediate density (IDL Sf 12-20) and low density lipoproteins (LDL Sf 0-12). Normal and hyperlipemic subjects were given tracer doses of 131I-labeled VLDL1 and 125I-labeled VLDL2 and the metabolism of apoB in VLDL1, VLDL2, IDL, and LDL was followed over a period of 13 days. VLDL1 apoB and VLDL2 apoB clearance curves had an initial shoulder, a rapid decay, and a 'tail' of slowly metabolized lipoprotein. ApoB derived from VLDL1 appeared in IDL over 10-50 h and exhibited bi-exponential decay that was attributed to the presence of two metabolically distinct species. A further compartment was required to explain the observation that a substantial proportion of apoB from VLDL2 appeared and disappeared from the IDL density range faster than apoB derived from VLDL1 delipidation. Both of the more rapidly removed IDL species gave rise to LDL apoB that was also modeled as a heterogeneous entity with two plasma compartments. The final model, which has much in common with previous versions (M. Berman et al. 1978. J. Lipid Res. 19: 38-56), a multi-step delipidation pathway and slowly metabolized remnant compartments in VLDL, incorporates parallel delipidation routes in VLDL2, IDL, and LDL. These parallel pathways linked kinetic heterogeneity in VLDL with that in IDL and LDL.