Premium
New model for kinetic studies of HDL metabolism in humans
Author(s) -
Chétiveaux M.,
Ouguerram K.,
Zair Y.,
Maugère P.,
Falconi I.,
Nazih H.,
Krempf M.
Publication year - 2004
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2004.01322.x
Subject(s) - fast protein liquid chromatography , chemistry , apolipoprotein b , cholesterol , chromatography , metabolism , leucine , medicine , endocrinology , biochemistry , high performance liquid chromatography , biology , amino acid
Background The aim of the study was to develop a new model for kinetic studies of Apolipoprotein A‐I of HDL (Apo A‐I‐HDL) labelled with stable isotope by using HDL subclasses isolated with fast protein liquid chromatography (FPLC). Materials and methods Apo A‐I‐HDL kinetics were studied by infusing [5.5.5– 2 H 3 ]‐leucine for 14 h in six healthy subjects. Preβ 1 and αHDL were separated by FPLC and total HDL by ultracentrifugation (HDL‐UC). Results The tracer‐to‐tracee ratios were higher in preβ 1 HDL than in HDL‐UC or αHDL. Leucine enrichments found in HDL‐UC were higher compared with αHDL, suggesting that HDL‐UC were composed of a mixture of Apo A‐I‐αHDL and Apo A‐I‐preβ 1 HDL. Kinetic analysis of data obtained from FPLC was achieved using a multicompartmental model, including a conversion between preβ 1 and αHDL compartments. The production rate of preβ 1 HDL was 7·72 ± 2·86 mg kg −1 d −1 (mean ± SD) . Preβ 1 HDL were converted to αHDL at a rate of 96·24 ± 42·99 pool d −1 , and the synthesis rate of preβ 1 HDL from αHDL was 10‐fold slower: 7·09 ± 4·51 pool d −1 . Apo A‐I‐FCR of HDL‐UC was estimated using a one‐compartment model (0·165 ± 0·074 pool d −1 ), and was higher but not significantly compared with FCR of Apo A‐I‐αHDL (0·112 ± 0·026 pool d −1 ) calculated with the new model. Conclusions This study reports for the first time a model involving enrichments of Apo A‐I in preβ 1 and αHDL which allowed the measure of Apo A‐I cycling within HDL fraction and will aid better understanding of kinetics of HDL in humans.