DEVELOPMENT AND APPLICATION OF A MULTICOMPARTMENTAL MODEL TO STUDY VERY-LOW-DENSITY LIPOPROTEIN SUBFRACTION METABOLISM

A multicompartmental model has been devised to explain apolipoprotein B (apoB) kinetics in very low density lipoprotein subfractions (VLDL(1) S-f 60-400 and VLDL(2) S-f 20-60), intermediate density (IDL S-f 12-20) and low density lipoproteins (LDL S-f 0-12). Normal and hyperlipemic subjects were given tracer doses of I-131-labeled VLDL(1) and I-125-labeled VLDL(2) and the metabolism of apoB in VLDL(1), VLDL(2), IDL, and LDL was followed over a period of 13 days. VLDL(1) apoB and VLDL(2) apoB clearance curves had an initial shoulder, a rapid decay, and a 'tail' of slowly metabolized lipoprotein. ApoB derived from VLDL(1) 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 VLDL(2) appeared and disappeared from the IDL density range faster than apoB derived from VLDL(1) 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 VLDL(2), IDL, and LDL. These parallel pathways linked kinetic heterogeneity in VLDL with that IDL and LDL.