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Journal of Lipid Research, Vol. 46, 58-67, January 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

A new combined multicompartmental model for apolipoprotein B-100 and triglyceride metabolism in VLDL subfractions

Martin Adiels^*, Chris Packard, Muriel J. Caslake, Philip Stewart, Aino Soro, Jukka Westerbacka, Bernt Wennberg^*, Sven-Olof Olofsson^**, Marja-Riitta Taskinen and Jan Borén^1,**

^* Mathematical Sciences, Chalmers University of Technology, 412 96 Göteborg, Sweden
Department of Pathological Biochemistry, Glasgow Royal Infirmary, G31 2ER Glasgow, United Kingdom
Division of Cardiology, Helsinki University Hospital, Biomedicum, 00029 Helsinki, Finland
^** Wallenberg Laboratory, Göteborg University, 413 25 Göteborg, Sweden

¹ To whom correspondence should be addressed. e-mail: jan.boren{at}wlab.gu.se

The use of stable isotopes in conjunction with compartmental modeling analysis has greatly facilitated studies of the metabolism of the apolipoprotein B (apoB)-containing lipoproteins in humans. The aim of this study was to develop a multicompartment model that allows us to simultaneously determine the kinetics of apoB and triglyceride (TG) in VLDL₁ and VLDL₂ after a bolus injection of [²H₃]leucine and [²H₅]glycerol and to follow the catabolism and transfer of the lipoprotein particles. Here, we describe the model and present the results of its application in a fasting steady-state situation in 17 subjects with lipid values representative of a Western population. Analysis of the correlations showed that plasma TG was determined by the VLDL₁ and VLDL₂ apoB and TG fractional catabolic rate. Furthermore, the model showed a linear correlation between VLDL₁ TG and apoB production. A novel observation was that VLDL TG entered the circulation within 21 min after its synthesis, whereas VLDL apoB entered the circulation after 33 min.

These observations are consistent with a sequential assembly model of VLDL and suggest that the TG is added to a primordial apoB-containing particle in the liver.

Supplementary key words very low density lipoprotein • kinetics • stable isotope • assembly

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