Effect of cholesteryl ester transfer protein (CETP) expression on diet-induced hyperlipidemias in transgenic rats.
OBJECTIVE
In order to determine the influence of the lipid status on the ability of cholesteryl ester transfer protein (CETP) to modify the plasma lipoprotein profile, the effect of hypercholesterolemia versus hypertriglyceridemia were compared in wild-type and CETP-transgenic (CETPTg) rats expressing CETP at a constant level.


RESULTS
Wild-type and CETPTg rats were fed either a chow diet, a high fat/high cholesterol (HF/HC) diet, or a sucrose diet. As compared to wild-type rats, CETPTg rats fed the standard chow exhibited lower high-density lipoproteins (HDL)-cholesterol concentration (-65%, p<0.01), but similar non-HDL-cholesterol concentrations. Both wild-type and CETPTg rats fed the HF/HC diet displayed pronounced increases in total and non-HDL-cholesterol levels, with no influence of CETP expression in this case. In contrast, the sucrose diet produced significant changes only in CETPTg rats which then exhibited a 82% increase in non-HDL-cholesterol in addition to a 80% reduction in HDL cholesterol when compared to sucrose-fed, wild-type rats (p<0.01 in both cases). The triglyceride to cholesterol ratio in very low-density lipoprotein (VLDL) was 10-fold lower in 'HF/HC' rats than in 'chow' and 'sucrose' rats (p<0.005 and p<0.01, respectively), and VLDL from 'HF/HC' animals were proven to constitute poor cholesteryl ester acceptors.


CONCLUSIONS
CETP expression modified dramatically the lipoprotein phenotype in 'sucrose' rats but not in 'HF/HC' rats. These observations suggest that a CETP inhibitor treatment is susceptible to produce profound changes in hypertriglyceridemia or combined hyperlipidemia.
Zak
Zoulika
Z
Laboratoire de Biochimie des Lipoprotéines, INSERM U498, Faculté de Médecine, BP 87900, Dijon Cedex 21033, France.
Gautier
Thomas
T
Dumont
Laure
L
Masson
David
D
Deckert
Valérie
V
Duverneuil
Linda
L
Pais De Barros
Jean-Paul
JP
Le Guern
Naig
N
Schneider
Martina
M
Moulin
Philippe
P
Bataillard
Alain
A
Lagrost
Laurent
L
D000821:Animal Feed; D000818:Animals; D030801:Animals, Genetically Modified; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000494:pharmacology*; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D004032:Diet; D006023:Glycoproteins / Q000096:biosynthesis* / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000235:genetics* / Q000503:physiopathology* / Q000662:veterinary; D008074:Lipoproteins / Q000097:blood*; D010641:Phenotype; D051381:Rats; D013395:Sucrose / Q000378:metabolism; D013549:Sweetening Agents / Q000378:metabolism; D014280:Triglycerides
D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008074:Lipoproteins; D013549:Sweetening Agents; D014280:Triglycerides; D013395:Sucrose