on July 8, 2004
Published online before print July 8, 2004, doi: 10.1161/01.ATV.0000137975.14996.df
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Submitted on May 6, 2004
Accepted on June 3, 2004
Interrelationships Between Human Apolipoprotein A-I and Apolipoproteins B-48 and B-100 Kinetics Using Stable Isotopes
Francine K. Welty *;
From the Lipid Metabolism Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Mass; the Division of Cardiology (F.K.W.), Beth Israel Deaconess Medical Center, and the School of Medicine and Pharmacology (P.H.R.B.), University of Western Australia, Perth, Australia.
* To whom correspondence should be addressed. E-mail: fwelty{at}bidmc.harvard.edu.
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 [5,5,5-2H3] 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.
Key words: apolipoprotein A-I • apolipoprotein B • lipoprotein metabolism • stable isotopes • HDL cholesterol
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