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Investigation of human apoB48 metabolism using a new, integrated non-steady-state model of apoB48 and apoB100 kinetics

Journal article
Authors Elias Björnson
C. J. Packard
Martin Adiels
L. Andersson
N. Matikainen
S. Soderlund
J. Kahri
Carina Sihlbom
Annika Thorsell
H. Zhou
M. R. Taskinen
Jan Borén
Published in Journal of Internal Medicine
Volume 285
Issue 5
Pages 562-577
ISSN 0954-6820
Publication year 2019
Published at Core Facilities, Proteomics
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 562-577
Language en
Links dx.doi.org/10.1111/joim.12877
Keywords apolipoprotein B48, kinetics, model, remnants, stable isotope, triglyceride-rich lipoproteins, apolipoprotein b-48 transport, of-function mutations, stable-isotope, obese subjects, c-iii, a-i, plasma, b-100, quantitation
Subject categories Clinical Medicine

Abstract

BackgroundTriglyceride-rich lipoproteins and their remnants have emerged as major risk factors for cardiovascular disease. New experimental approaches are required that permit simultaneous investigation of the dynamics of chylomicrons (CM) and apoB48 metabolism and of apoB100 in very low-density lipoproteins (VLDL). MethodsMass spectrometric techniques were used to determine the masses and tracer enrichments of apoB48 in the CM, VLDL1 and VLDL2 density intervals. An integrated non-steady-state multicompartmental model was constructed to describe the metabolism of apoB48- and apoB100-containing lipoproteins following a fat-rich meal, as well as during prolonged fasting. ResultsThe kinetic model described the metabolism of apoB48 in CM, VLDL1 and VLDL2. It predicted a low level of basal apoB48 secretion and, during fat absorption, an increment in apoB48 release into not only CM but also directly into VLDL1 and VLDL2. ApoB48 particles with a long residence time were present in VLDL, and in subjects with high plasma triglycerides, these lipoproteins contributed to apoB48 measured during fasting conditions. Basal apoB48 secretion was about 50mgday(-1), and the increment during absorption was about 230mgday(-1). The fractional catabolic rates for apoB48 in VLDL1 and VLDL2 were substantially lower than for apoB48 in CM. DiscussionThis novel non-steady-state model integrates the metabolic properties of both apoB100 and apoB48 and the kinetics of triglyceride. The model is physiologically relevant and provides insight not only into apoB48 release in the basal and postabsorptive states but also into the contribution of the intestine to VLDL pool size and kinetics.

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