Interrelationships Between Human Apolipoprotein A-I and Apolipoproteins B-48 and B-100 Kinetics Using Stable Isotopes

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Abstract
Objective— Our purpose was to determine the relationship between apolipoprotein (apo) A-I and apoB-48 and apoB-100 metabolism in moderately hypercholesterolemic humans. Methods and Results— The kinetics of apoA-I within high-density lipoprotein (HDL), apoB-48 and apoB-100 within triglyceride-rich lipoproteins, and apoB-100 within intermediate-density lipoprotein and low density-lipoprotein (LDL) were examined with a primed constant infusion of [5,5,5- 2 H 3 ] leucine in the fed state (hourly feeding) in 23 subjects after consumption of a 36% total fat diet. Lipoproteins were isolated by ultracentrifugation; apolipoproteins by SDS-PAGE gels; and isotope enrichment assessed by gas chromatograph/mass spectrometry. Kinetic parameters were calculated by multicompartmental modeling of the data with SAAM II. ApoA-I production rate (PR) was correlated with LDL apoB-100 pool size (PS; r =0.49; P =0.017) and LDL cholesterol ( r =0.61; P =0.002), whereas apoA-I fractional catabolic rate (FCR) was inversely correlated with apoB-48 FCR ( r =−0.40; P =0.05) but not with very low-density lipoprotein apoB-100 FCR. Conclusions— Two links exist between apoA-I and apoB kinetics: 1) when LDL apoB-100 PS is high, there is increased apoA-I PR; and 2) delayed chylomicron remnant clearance (represented by apoB-48 FCR) is associated with enhanced apoA-I FCR, a finding indicating that alterations in intestinal lipoproteins may be more important in determining HDL cholesterol levels than changes in liver lipoproteins.