Journal of Lipid Research, Vol. 19, 38-56, January 1978
Copyright © 1978 by Lipid Research, Inc.

Metabolism of apoB and apoC lipoproteins in man: kinetic studies in normal and hyperlipoproteinemic subjects

Mones Berman , Marshall Hall III , Robert I. Levy , Shlomo Eisenberg , David W. Bilheimer , Robert D. Phair , and Robert H. Goebel

Laboratory of Theoretical Biology, DCBD, National Cancer Institute and Molecular Disease Branch, National Heart and Lung Institute, National Institutes of Health, Bethesda, MD 20014

The kinetics of apolipoproteins B and C were studied in 14 normal and hyperlipoproteinemic subjects after injection of exogenously ¹²⁵I-labeled very low density lipoprotein (VLDL) particles. Plasma radioactivities of apoB and apoC were determined over a period of 4 days in VLDL (d < 1.006) and total radioactivity in intermediate (IDL) (1.006 < d < 1.019), low (LDL) (1.019 < d < 1.063), and high (HDL) (1.063 < d < 1.21) density lipoproteins. The data were analyzed by the use of a model, developed mostly from these data, with the following results. The VLDL particle undergoes a series of incremental density changes, most likely due to a number of delipidation steps, during which apoB stays with the particle until the density reaches the IDL range. There is, however, a loss of apoC associated with these delipidation steps. In our normal subjects, all IDL apoB eventually becomes LDL. In our hyperlipemic subjects some of the apoB on IDL is also degraded directly. The apoC lost by VLDL and IDL recycles to HDL, and most of it is picked up again by newly synthesized VLDL. There is a slowdown of the stepwise delipidation process in all hyperlipemic individuals studied. Three additional features became apparent in the type III subjects. First, there is a significant increase (a factor of 2 compared to normal) in the apoB synthesis rate by way of VLDL; second, there is an induced direct apoB synthesis pathway by way of IDL (and/or LDL); third, a bypass of the regular stepwise VLDL delipidation pathway is induced by which VLDL particles lose apoC but none of their apoB, thereby forming a new particle with metabolic properties similar to LDL, but with a density still in the VLDL density range. Two type III patients treated with nicotinic acid and clofibrate showed a sharp decrease in their VLDL apoB synthesis rates. This was somewhat compensated by an increased IDL apoB synthesis rate. A type I patient on a medium chain triglyceride diet also showed a number of metabolic changes, including reduced VLDL apoB synthesis and the induction of considerable IDL and/or LDL apoB synthesis.

Supplementary key words mathematical models • apolipoproteins • VLDL • LDL • IDL • HDL • compartmental models • type III hyperlipoproteinemia

Submitted on October 28, 1976
Revised on March 18, 1977
Accepted on May 27, 1977

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