A new combined multicompartmental model for apolipoprotein B-100 and triglyceride metabolism in VLDL subfractions.
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 VLDL(1) and VLDL(2) after a bolus injection of [(2)H(3)]leucine and [(2)H(5)]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 VLDL(1) and VLDL(2) apoB and TG fractional catabolic rate. Furthermore, the model showed a linear correlation between VLDL(1) 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.
Mathematical Sciences, Chalmers University of Technology, 412 96 Göteborg, Sweden.
Martin
M
Adiels
Chris
C
Packard
Muriel J
MJ
Caslake
Philip
P
Stewart
Aino
A
Soro
Jukka
J
Westerbacka
Bernt
B
Wennberg
Sven-Olof
SO
Olofsson
Marja-Riitta
MR
Taskinen
Jan
J
Borén
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000096:biosynthesis / Q000378:metabolism*; D003903:Deuterium / Q000008:administration & dosage / Q000378:metabolism; D005990:Glycerol / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007930:Leucine / Q000008:administration & dosage / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000096:biosynthesis / Q000378:metabolism*; D008954:Models, Biological; D021381:Protein Transport; D014280:Triglycerides / Q000096:biosynthesis / Q000378:metabolism*
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D003903:Deuterium; D007930:Leucine; D005990:Glycerol