Apolipoprotein B metabolism and the distribution of VLDL and LDL subfractions

Apolipoprotein B (apoB) metabolism was investigated in 20 men with plasma t riglyceride 0.66-2.40 mmol/l and plasma cholesterol 3.95-6.95 mmol/l. Kinet ics of VLDL1 (S-f 60-400), VLDL2 (S-f 20-60), IDL (S-f 12-20), and LDL (S-f 0-12) apoB were analyzed using a trideuterated leucine tracer and a multic ompartmental model which allowed input into each fraction. VLDL1 apoB produ ction varied widely (from 5.4 to 26.6 mg/kg/d) as did VLDL2 apoB production (from 0.18 to 8.4 mg/kg/d) but the two were not correlated. IDL plus LDL a poB direct production accounted for up to half of total apoB production and was inversely related to plasma triglyceride (r = -0.54, P = 0.009), Perce nt of direct apoB production into the IDL/ LDL density range (r = 0.50, P < 0.02) was positively related to the LDL apoB fractional catabolic rate (FC R), Plasma triglyceride in these subjects was determined principally by VLD L1 and VLDL2 apoB fractional transfer rates (FTR), i.e., lipolysis, IDL apo B concentration was regulated mainly by the IDL to LDL FTR (r = -0.71, P < 0.0001). LDL apoB concentration correlated with VLDL2 apoB production (r = 0.48, P = 0.018) and the LDL FCR (r = -0.77, P < 0.001) but not with VLDL1, IDL, or LDL apoB production. Subjects with predominantly small, dense LDL (pattern B) had lower VLDL1 and VLDL2 apoB FTRs, higher VLDL2 apoB producti on, and a lower LDL apoB FCR than those with large LDL (pattern A). jlr Thu s, the metabolic conditions that favored appearance of small, dense LDL wer e diminished lipolysis of VLDL, resulting in a raised plasma triglyceride a bove the putative threshold of 1.5 mmol/l, and a prolonged residence time f or LDL, This latter condition presumably permitted sufficient time for the processes of lipid exchange and lipolysis to generate small LDL particles.