Interrelationships between human apolipoprotein A-I and apolipoproteins B-48 and B-100 kinetics using stable isotopes.
OBJECTIVE
Our purpose was to determine the relationship between apolipoprotein (apo) A-I and apoB-48 and apoB-100 metabolism in moderately hypercholesterolemic humans.


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. Using stable isotopes in humans, 2 links were observed 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 is associated with enhanced apoA-I FCR, indicating that alterations in intestinal lipoproteins may be more important in determining HDL-C levels than changes in liver lipoprotein particles.
Welty
Francine K
FK
Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center at Tufts University, 711 Washington St, Boston, MA 02111, USA. fwelty@bidmc.harvard.edu
Lichtenstein
Alice H
AH
Barrett
P Hugh R
PH
Dolnikowski
Gregory G
GG
Schaefer
Ernst J
EJ
D000368:Aged; D000369:Aged, 80 and over; D016632:Apolipoprotein A-I / Q000097:blood*; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D002914:Chylomicrons / Q000097:blood; D004435:Eating; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood*; D007700:Kinetics; D007930:Leucine / Q000493:pharmacokinetics; D008074:Lipoproteins / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D008954:Models, Biological
D016632:Apolipoprotein A-I; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D002914:Chylomicrons; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D007930:Leucine