ACCUMULATION OF LARGE VERY-LOW-DENSITY LIPOPROTEIN IN PLASMA DURING INTRAVENOUS-INFUSION OF A CHYLOMICRON-LIKE TRIGLYCERIDE EMULSION REFLECTS COMPETITION FOR A COMMON LIPOLYTIC PATHWAY

Very low density lipoproteins (VLDL) are produced in the liver and con tain apolipoprotein (apo) B-100 and endogenous lipids. By contrast, in gestion of fat leads to formation of chylomicrons containing apoB-48 s ecreted from the intestine. In this study, a 60-min intravenous infusi on of a chylomicron-like triglyceride emulsion was given to healthy yo ung men to examine whether competition between chylomicrons and VLDL f or the same lipolytic pathway explains the increase in VLDL seen after meals. The responses of two major VLDL subfractions were determined b y measuring the concentrations of apoB-100 in fractions of triglycerid e-rich lipoproteins with Svedberg flotation rates of 60-400 (large VLD L) and 20-60 (small VLDL) that were separated from plasma by density g radient ultracentrifugation. A threefold elevation in plasma triglycer ides was observed during the infusion together with a consistent linea r increase of large VLDL. The rate at which large VLDL accumulated in plasma differed markedly among individuals and-was not enhanced by dou bling of the infusion rate. The response of small VLDL was more hetero geneous; however, a decrease was seen in most subjects, The combined p attern for the two VLDL species is what would be expected if large VLD L particles are the precursors of smaller VLDL species and if lipolysi s of large VLDL is inhibited through competition from the triglyceride emulsion. The extent to which the triglyceride emulsion inhibited the lipolysis of VLDL and/or influenced the synthesis rate of large VLDL was estimated from simultaneous stable isotope studies. The emulsion c aused a 75-90% block of the conversion of large VLDL apoB to small VLD L apoB and there was no sign of enhanced synthesis of large VLDL after infusion of the triglyceride emulsion. The corollary of these finding s is that chylomicrons and their remnants impede the normal lipolytic degradation of VLDL and could thereby be indirectly implicated in the generation of atherogenic remnant lipoproteins.