The metabolic heterogeneity of human very low density lipoprotein triglyceride

Abstract

Very low density lipoprotein (VLDL) particles are heterogeneous with respect to size and composition. However, in describing its kinetics, VLDL is often treated as a homogeneous pool. The present studies show that this is not the case. We examined the kinetics of triglyceride in three ultracentrifugally separated VLDL subfractions and in a fraction containing intermediate- and low-density lipoprotein (IDL-LDL). 2- 3H-Glycerol, given intravenously as a bolus injection or as a constant infusion, was used to label the triglyceride endogenously. Following the bolus of 3H-glycerol, the triglyceride specific activity peaked soonest in the largest lightest VLDL subfraction and latest in the smallest heaviest VLDL subfraction. The subsequent decline of specific activity was fastest for large VLDL and slowest for small VLDL. Comparing the curves of IDL-LDL and those of the VLDL subfractions showed that the smallest VLDL could not be the only presursor for the IDL-LDL triglyceride. During a constant infusion of 3H-glycerol the plateau specific activities of the triglyceride in the VLDL subfractions were 3.5%–5.0% that of plasma glycerol. These data indicate that relatively little VLDL triglyceride glycerol was derived directly from plasma glycerol. Furthermore, as the specific activity in large VLDL was less than that in small VLDL, the former could not be the only precursor for the latter. These studies show that VLDL is not metabolized in a homogeneous fashion. This heterogeneity may introduce complexities into the description of VLDL kinetics. The data do not exclude the existence of a cascade from large VLDL to small VLDL, and thence to IDL and LDL; rather, they indicate that this is not the only route of VLDL metabolism and that the entire spectrum of VLDL particles may be produced and degraded directly.