HDL biology
CETP transgenic rats show dramatic lipid shifts on a sucrose diet but not on a high-fat/high-cholesterol diet (Atherosclerosis 2005)
Original title: Effect of cholesteryl ester transfer protein (CETP) expression on diet-induced hyperlipidemias in transgenic rats
Researchers compared wild-type and CETP-transgenic (CETPTg) rats fed chow, a high fat/high cholesterol (HF/HC) diet, or a sucrose diet to test how lipid status affects the ability of CETP to modify plasma lipoprotein profiles. On standard chow, CETPTg rats had 65% lower HDL cholesterol than wild-type rats (p<0.01) but similar non-HDL cholesterol. Both genotypes showed pronounced increases in total and non-HDL cholesterol on the HF/HC diet, with no additional effect of CETP expression, but the sucrose diet produced significant changes only in CETPTg rats, which showed an 82% increase in non-HDL cholesterol and an 80% reduction in HDL cholesterol versus sucrose-fed wild-type rats (p<0.01 for both). VLDL triglyceride-to-cholesterol ratio was 10-fold lower in HF/HC rats than in chow or sucrose rats, and HF/HC-derived VLDL proved to be poor cholesteryl ester acceptors. The authors conclude CETP expression dramatically altered the lipoprotein phenotype in sucrose-fed but not HF/HC-fed rats, suggesting CETP inhibitor treatment could produce profound lipid changes specifically in hypertriglyceridemia or combined hyperlipidemia.
Original abstract
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.
Methods And 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.