Metabolism of cholesterol ester of apolipoprotein B100-containing lipoproteins in dogs: evidence for disregarding cholesterol ester transfer.
BACKGROUND
It has been shown that dogs exhibit no cholesterol ester transfer protein (CETP) activity in vitro, in contrast to humans. The aim of our study was to determine modalities of in vivo plasma cholesterol ester turnover in this species, using a kinetic approach with stable isotopes.


METHODS
Kinetics of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) were studied in seven adult male Beagle dogs using a dual isotope approach through endogenous labelling of both their cholesterol moiety and their protein moiety. A primed constant infusion of both [1,2(13)C]acetate and [5,5,5-2H3]leucine enabled us to obtain measurable deuterium enrichments by gas chromatography-mass spectrometry for plasma leucine and apoB100, as well as measurable 13C enrichment by gas chromatography-combustion-isotopic ratio mass spectrometry for unesterified cholesterol and cholesterol ester in the VLDL and LDL. Two identical multicompartmental models (SAAM II) were used together for the analysis of tracer kinetics' data of proteins and cholesterol.


RESULTS
Characterization of the apoB100-containing lipoprotein cholesterol ester model allowed determination of kinetic parameters of VLDL and LDL cholesterol ester metabolism. We succeeded in modelling VLDL and LDL cholesterol ester metabolism and apoB100 metabolism simultaneously. Fractional catabolic rate (FCR) of apoB100 and CE had the same values. Introducing cholesterol ester transfer between lipoproteins in the model did not significantly improve the fit. Total VLDL FCR was 2.97 +/- 01.47 h(-1). Approximately one-quarter corresponded to the direct removal of VLDL (0.81 +/- 00.34 h(-1)) and the remaining three-quarters corresponded to the fraction of VLDL converted to LDL, which represented a conversion of VLDL into LDL of 2.16 +/- 01.16 h(-1). Low-density lipoproteins were produced exclusively from VLDL conversion and were then removed (0.031 +/- 0.004 h(-1)) from plasma.


CONCLUSIONS
These kinetic data showed that VLDL cholesterol ester and LDL cholesterol ester metabolism followed VLDL and LDL apoB100 metabolism, and that consequently there is no in vivo transfer of cholesterol ester in dogs.
Centre de Recherche en Nutrition Humaine, INSERM U539, CHU Nantes, France.
E
E
Bailhache
F
F
Briand
P
P
Nguyen
M
M
Krempf
T
T
Magot
K
K
Ouguerram
D000818:Animals; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000378:metabolism*; D002849:Chromatography, Gas; D004285:Dogs; D006023:Glycoproteins / Q000378:metabolism*; D007930:Leucine / Q000097:blood; D008077:Lipoproteins, LDL / Q000493:pharmacokinetics*; D008079:Lipoproteins, VLDL / Q000493:pharmacokinetics*; D008297:Male
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D007930:Leucine