Metabolism of apolipoprotein B in large triglyceride-rich very low density lipoproteins of normal and hypertriglyceridemic subjects

The metabolic fate of very low density lipoprotein can be examined by following the transit of its apolipoprotein B moiety through the delipidation cascade, which leads to low density lipoprotein. In this study we have used cumulative flotation ultracentrifugation to follow the metabolism of various lipoprotein subclasses that participate in this process in normal, hypertriglyceridemic (Type IV), and dysbetalipoproteinemic (Type III) subjects. Large triglyceride-rich very low density lipoproteins of Svedberg units of flotation (S(f)) 100-400 were converted virtually quantitatively in normal subjects to smalller S(f) 12-100 remnant particles. Only a minor fraction appeared thereafter in low density lipoproteins (S(f) 0-12), most being removed directly from the plasma. Type IV hyperlipoproteinemic individuals converted the larger S(f) 100-400 very low density lipoproteins to intermediate particles at ~50% of the control rate but thereafter their metabolism was normal (fractional clearance of S(f) 12-100 particles in controls, 1.29 ± 0.23 pools/d; in Type IV hypertriglyceridemics, 1.38 ± 0.23 pools/d; n = 4 in each case). Since the apolipoprotein B in large triglyceride-rich particles did not contribute significantly to the mass of the low density lipoprotein apoprotein pool, the latter must come largely from another source. This was examined by following the metabolic fate of small very low density lipoproteins of S(f) 20-60 or of the total lipoprotein spectrum of d < 1.006 kg/liter (approximate S(f) 20-400). The small particles were rapidly and substantially converted to low density lipoproteins, suggesting that the major precursor of the latter was to be found in this density range. Whereas only 10% of apolipoproteins B in S(f) 100-400 lipoproteins reached the low density lipoprotein flotation range, >40% of S(f) 20-100 B protein eventually appeared in S(f) 0-12 particles; and when very low density lipoprotein of d < 1.006 kg/liter is used as a tracer of apolipoprotein B metabolism it is primarily this population of small very low density lipoprotein particles in the S(f) 12-100 flotation range that is labeled. A detailed examination was made of apolipoprotein B metabolism in three dysbetalipoproteinemic subjects. The plasma clearance curves of their S(f) 100-400 lipoproteins were distinctly biphasic. The quickly decaying component converted rapidly into remnants of S(f) 20-60 at a near normal rate (0.56 vs. 0.62 pools/d in normal subjects). Its subsequent processing, however, was retarded. The more slowly catabolized fraction, comprising 30% of the total apolipoprotein B radioactivity, had no counterpart in normal or Type IV hyperlipoproteinemic individuals. These data, taken together, suggest that the very low density lipoprotein consists of a complex mixture of particles with different origins and fates. Within the S(f) 20-100 flotation range there are at least two subcomponents. One represents remnants of larger triglyceride-rich particles which are catabolized slowly and feeds little apolipoprotein B into low density lipoprotein. The other is apparently secreted directly into this flotation interval and transfers significant amounts of B protein rapidly into S(f) 0-12 lipoproteins.