A new model of human VLDL metabolism based on simultaneous studies of its apo B and triglyceride

Abstract

Previous studies which separately examined the behavior of the B apolipoprotein and of the triglyceride of VLDL had raised the possibility that each was metabolized in a different manner. The present studies have explored this possibility by simultaneously studying each of these VLDL constituents in thirteen humans. 125I-labeled Sf 60–400 lipoproteins were injected. The fate of their apo B (a reflection of the metabolism of the lipoprotein particle) was followed in this, and in the smaller Sf 12–60 lipoproteins. In everyone, the larger particle was catabolized to the smaller one. Furthermore, the smaller particle was derived exclusively from the larger one. The behavior of the lipoproteins' triglyceride was examined by following the specific activity of 3H-triglyceride which had been endogenously labelled by injecting 2- 3H-glycerol. Some of the larger lipoproteins' triglyceride appeared in the smaller particles. However, in contrast to the apo B, the triglyceride in the smaller particle was not derived exclusively from that in the larger particle. In eleven subjects, the triglyceride specific activity curves above demonstrated that some of the triglyceride entered the smaller circulating particle from a source other than the large particle. A comparison of the times at which the peaks of the triglyceride and apo B specific activities occurred in the Sf 12–60 fraction also showed that some of the triglyceride entered the smaller particles independent of the catabolism of the larger particles in seven of these eleven subjects and in one of the remaining two. Thus VLDL appears to enter the circulation as a large particle which undergoes a catabolism to a progressively smaller particle, the latter being derived exclusively from the former. By contrast, some of the triglyceride enters directly into pre-existing circulating triglyceride rich lipoproteins by a process which is independant of this catabolic cascade.