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Interrelationships between human apolipoprotein A-I and apolipoproteins B-48 and B-100 kinetics using stable isotopes.
Arterioscler Thromb Vasc Biol. 2004 Sep; 24(9):1703-7.AT

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. 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.

Authors+Show Affiliations

Welty 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 AH
No affiliation info available
Barrett PH
No affiliation info available
Dolnikowski GG
No affiliation info available
Schaefer EJ
No affiliation info available

MeSH

AgedAged, 80 and overApolipoprotein A-IApolipoprotein B-100Apolipoprotein B-48Apolipoproteins BCholesterol, HDLChylomicronsEatingFemaleHumansHypercholesterolemiaKineticsLeucineLipoproteinsLipoproteins, HDLLipoproteins, IDLLipoproteins, LDLLipoproteins, VLDLMaleMiddle AgedModels, Biological

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15242863

Clinical Trial Links

Mechanisms of Low Levels of Apolipoprotein B

Citation

Welty, Francine K., et al. "Interrelationships Between Human Apolipoprotein A-I and Apolipoproteins B-48 and B-100 Kinetics Using Stable Isotopes." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 9, 2004, pp. 1703-7.
Welty FK, Lichtenstein AH, Barrett PH, et al. Interrelationships between human apolipoprotein A-I and apolipoproteins B-48 and B-100 kinetics using stable isotopes. Arterioscler Thromb Vasc Biol. 2004;24(9):1703-7.
Welty, F. K., Lichtenstein, A. H., Barrett, P. H., Dolnikowski, G. G., & Schaefer, E. J. (2004). Interrelationships between human apolipoprotein A-I and apolipoproteins B-48 and B-100 kinetics using stable isotopes. Arteriosclerosis, Thrombosis, and Vascular Biology, 24(9), 1703-7.
Welty FK, et al. Interrelationships Between Human Apolipoprotein A-I and Apolipoproteins B-48 and B-100 Kinetics Using Stable Isotopes. Arterioscler Thromb Vasc Biol. 2004;24(9):1703-7. PubMed PMID: 15242863.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interrelationships between human apolipoprotein A-I and apolipoproteins B-48 and B-100 kinetics using stable isotopes. AU - Welty,Francine K, AU - Lichtenstein,Alice H, AU - Barrett,P Hugh R, AU - Dolnikowski,Gregory G, AU - Schaefer,Ernst J, Y1 - 2004/07/08/ PY - 2004/7/10/pubmed PY - 2005/4/6/medline PY - 2004/7/10/entrez SP - 1703 EP - 7 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler Thromb Vasc Biol VL - 24 IS - 9 N2 - 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. 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. SN - 1524-4636 UR - https://www.unboundmedicine.com/medline/citation/15242863/Interrelationships_between_human_apolipoprotein_A_I_and_apolipoproteins_B_48_and_B_100_kinetics_using_stable_isotopes_ DB - PRIME DP - Unbound Medicine ER -