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Apolipoprotein B (apoB) metabolism was investigated in 20 men with plasma triglyceride 0.66–2.40 mmol/l and plasma cholesterol 3.95–6.95 mmol/l. Kinetics of VLDL1 (Sf 60–400), VLDL2 (Sf 20–60), IDL (Sf 12–20), and LDL (Sf 0–12) apoB were analyzed using a trideuterated leucine tracer and a multicompartmental model which allowed input into each fraction. VLDL1 apoB production 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 apoB direct production accounted for up to half of total apoB production and was inversely related to plasma triglyceride (r = −0.54, P = 0.009). Percent 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 (FCR). Plasma triglyceride in these subjects was determined principally by VLDL1 and VLDL2 apoB fractional transfer rates (FTR), i.e., lipolysis. IDL apoB 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 production, and a lower LDL apoB FCR than those with large LDL (pattern A). Thus, the metabolic conditions that favored appearance of small, dense LDL were diminished lipolysis of VLDL, resulting in a raised plasma triglyceride above the putative threshold of 1.5 mmol/l, and a prolonged residence time for LDL. This latter condition presumably permitted sufficient time for the processes of lipid exchange and lipolysis to generate small LDL particles. —Packard, C. J., T. Demant, J. P. Stewart, D. Bedford, M. J. Caslake, G. Schwertfeger, A. Bedynek, J. Shepherd, and D. Seidel. Apolipoprotein B metabolism and the distribution of VLDL and LDL subfractions.

Kinetics of apo B and apo AI were assessed in 8 patients with mixed hyperlipidemia at baseline and after 8 weeks of atorvastatin 80 mg q.d. and micronised fenofibrate 200 mg q.d. in a cross-over study. Both increased hepatic production and decreased catabolism of VLDL accounted for elevated cholesterol and triglyceride concentrations at baseline. Atorvastatin significantly decreased triglyceride, total, VLDL and LDL cholesterol and apo B concentrations (−65%, −36%, −57%, −40% and −33%, respectively, P < 0.05). Kinetic analysis revealed that atorvastatin stimulated the catabolism of apo B containing lipoproteins, enhanced the delipidation of VLDL1 and decreased VLDL1 production. Fenofibrate lowered triglycerides and VLDL cholesterol (−57% and −64%, respectively, P < 0.05) due to enhanced delipidation of VLDL1 and VLDL2 and increased VLDL1 catabolism. Changes of HDL particle composition accounted for the increase of HDL cholesterol during atorvastatin and fenofibrate (18% and 23%, P < 0.01). Only fenofibrate increased apo AI concentrations through enhanced apo AI synthesis (45%, P < 0.05).We conclude that atorvastatin exerts additional beneficial effects on the metabolism of apo B containing lipoproteins unrelated to an increase in LDL receptor activity. Fenofibrate but not atorvastatin increases apo AI production and plasma turnover.