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

E. Björnson, C. J. Packard, M. Adiels, L. Andersson, Niina Matikainen, S. Söderlund, J. Kahri, C. Sihlbom, A. Thorsell, H. Zhou, M.-R. Taskinen, J. Borén

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Background Triglyceride-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). Methods Mass 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. Results The 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 50 mg day?1, and the increment during absorption was about 230 mg day?1. The fractional catabolic rates for apoB48 in VLDL1 and VLDL2 were substantially lower than for apoB48 in CM. Discussion This 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.
Original languageEnglish
JournalJournal of internal medicine
Volume285
Issue number5
Pages (from-to)562-577
Number of pages16
ISSN0954-6820
DOIs
Publication statusPublished - 18 Feb 2019
MoE publication typeA1 Journal article-refereed

Fields of Science

  • apolipoprotein B48
  • kinetics
  • model
  • remnants
  • stable isotope

Cite this

Björnson, E. ; Packard, C. J. ; Adiels, M. ; Andersson, L. ; Matikainen, Niina ; Söderlund, S. ; Kahri, J. ; Sihlbom, C. ; Thorsell, A. ; Zhou, H. ; Taskinen, M.-R. ; Borén, J. / Investigation of human apoB48 metabolism using a new, integrated non-steady-state model of apoB48 and apoB100 kinetics. In: Journal of internal medicine. 2019 ; Vol. 285, No. 5. pp. 562-577.
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title = "Investigation of human apoB48 metabolism using a new, integrated non-steady-state model of apoB48 and apoB100 kinetics",
abstract = "Background Triglyceride-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). Methods Mass 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. Results The 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 50 mg day?1, and the increment during absorption was about 230 mg day?1. The fractional catabolic rates for apoB48 in VLDL1 and VLDL2 were substantially lower than for apoB48 in CM. Discussion This 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.",
keywords = "apolipoprotein B48, kinetics, model, remnants, stable isotope",
author = "E. Bj{\"o}rnson and Packard, {C. J.} and M. Adiels and L. Andersson and Niina Matikainen and S. S{\"o}derlund and J. Kahri and C. Sihlbom and A. Thorsell and H. Zhou and M.-R. Taskinen and J. Bor{\'e}n",
year = "2019",
month = "2",
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Investigation of human apoB48 metabolism using a new, integrated non-steady-state model of apoB48 and apoB100 kinetics. / Björnson, E.; Packard, C. J.; Adiels, M.; Andersson, L.; Matikainen, Niina; Söderlund, S.; Kahri, J.; Sihlbom, C.; Thorsell, A.; Zhou, H.; Taskinen, M.-R.; Borén, J.

In: Journal of internal medicine, Vol. 285, No. 5, 18.02.2019, p. 562-577.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Investigation of human apoB48 metabolism using a new, integrated non-steady-state model of apoB48 and apoB100 kinetics

AU - Björnson, E.

AU - Packard, C. J.

AU - Adiels, M.

AU - Andersson, L.

AU - Matikainen, Niina

AU - Söderlund, S.

AU - Kahri, J.

AU - Sihlbom, C.

AU - Thorsell, A.

AU - Zhou, H.

AU - Taskinen, M.-R.

AU - Borén, J.

PY - 2019/2/18

Y1 - 2019/2/18

N2 - Background Triglyceride-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). Methods Mass 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. Results The 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 50 mg day?1, and the increment during absorption was about 230 mg day?1. The fractional catabolic rates for apoB48 in VLDL1 and VLDL2 were substantially lower than for apoB48 in CM. Discussion This 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.

AB - Background Triglyceride-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). Methods Mass 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. Results The 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 50 mg day?1, and the increment during absorption was about 230 mg day?1. The fractional catabolic rates for apoB48 in VLDL1 and VLDL2 were substantially lower than for apoB48 in CM. Discussion This 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.

KW - apolipoprotein B48

KW - kinetics

KW - model

KW - remnants

KW - stable isotope

U2 - 10.1111/joim.12877

DO - 10.1111/joim.12877

M3 - Article

VL - 285

SP - 562

EP - 577

JO - Journal of internal medicine

JF - Journal of internal medicine

SN - 0954-6820

IS - 5

ER -