Evidence for heterogeneity of low-density lipoprotein metabolism in the cynomolgus monkey

Abstract

Preliminary studies were performed to establish whether there was kinetic heterogeneity in the metabolism of subclasses of low-density lipoproteins (LDL) in the cynomolgus monkey. Previous studies of the effects of inhibition of hepatic triglyceride lipase in this species had shown an increase in the mass of lighter LDL ( S f ⪢ 9) and a decrease in the mass of denser LDL. LDL (1.019 < d < 1.063) were subdivided into two subfractions LDL, (1.019 < d < 1.035) and LDL 2 (1.035 < d < 1.063) by ultracentrifugation. The lipoproteins in these these two fractions could be shown to have different floatation by analytic and isopycnic ultracentrifugation. When tracer amounts of homologous 125I-labeled very-low-density lipoproteins (VLDL) were injected into chow-fed cynomolgus monkeys, apoB radioactivity appeared in LDL 1 prior to its appearance in LDL 2. [ 125I)LDL 1 injected into the monkey was removed from the LDL 1 density subclass with a half-life of 5.5–10.3 h. Much of the radioactivity injected as LDL 1 was converted to denser LDL (LDL 2). Labeled LDL 2 injected into the monkey was not converted to LDL 1. Thus, at least two kinetically distinct subpopulations of LDL circulate in the plasma of this species. The lighter LDL is to a large extent a metabolic precursor of the more dense LDL (LDL 2).