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. 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.