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

Björnson, E. et al. (2019) Investigation of human apoB48 metabolism using a new, integrated non‐steady‐state model of apoB48 and apoB100 kinetics. Journal of Internal Medicine, 285(5), pp. 562-577. (doi: 10.1111/joim.12877) (PMID:30779243)

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.

• Item Type: Articles
• Additional Information: This project was funded by grants from Swedish HeartLung Foundation, Swedish Diabetes Foundation, Swedish Research Council and Sahlgrenska University Hospital, Sigrid Juselius Foundation, Helsinki University Hospital Research funds, EU project RESOLVE and Finnish Heart Foundation.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Packard, Professor Chris
• Authors: Björnson, E., Packard, C.J., Adiels, M., Andersson, L., Matikainen, N., Söderlund, S., Kahri, J., Sihlbom, C., Thorsell, A., Zhou, H., Taskinen, M.‐R., and Borén, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Journal of Internal Medicine
• Publisher: Wiley
• ISSN: 0954-6820
• ISSN (Online): 1365-2796
• Published Online: 18 February 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Journal of Internal Medicine 285(5):562-577
• Publisher Policy: Reproduced under a Creative Commons license