Genetics
Human CETP expression completely prevents diet-induced atherosclerotic lesions in diabetic obese db/db mice (Arterioscler Thromb Vasc Biol 2003)
Original title: Cholesteryl ester transfer protein expression prevents diet-induced atherosclerotic lesions in male db/db mice
Since plasma CETP is depressed in diabetic obese patients compared with nondiabetic obese counterparts, potentially contributing to their more atherogenic lipoprotein profile, this study tested the effect of CETP expression on atherosclerosis in the db/db mouse model of diabetic obesity. Human CETP minigene transgenic mice were crossed with db/db mice, producing CETP, db, and db/CETP offspring fed an atherogenic diet for 16 weeks, with the proximal aorta examined for atherosclerotic plaques. Nine of 11 db mice developed intimal lesions with a mean area of 26 098 square micrometers, whereas no lesions larger than 1,000 square micrometers were observed in db/CETP or CETP mice. CETP-expressing mice had lower circulating cholesterol than db mice, with FPLC fractionation showing this difference was primarily due to lower VLDL and LDL cholesterol. The authors conclude that human CETP expression prevented diet-induced atherosclerotic lesion formation in this diabetic obesity model, suggesting an antiatherogenic effect of CETP in this context.
Original abstract
Objective: Accompanying more atherogenic lipoprotein profiles and an increased incidence of atherosclerosis, plasma cholesteryl ester transfer protein (CETP) is depressed in diabetic obese patients compared with nondiabetic obese counterparts. The depressed levels of CETP in the plasma of diabetic obese individuals may contribute to the development of an atherogenic lipoprotein profile and atherogenesis. We have examined the effect of CETP expression on vascular health in the db/db model of diabetic obesity.
Methods And Results: Transgenic mice expressing the human CETP minigene were crossed with db/db strain, and 3 groups of offspring (CETP, db, and db/CETP) were placed on an atherogenic diet for 16 weeks. The proximal aorta was then excised and examined for the presence of atherosclerotic plaques. In db mice, 9 of 11 had intimal lesions with a mean area of 26 098+/-7486 microm2. No lesions greater than 1000 microm2 were observed in db/CETP or CETP mice. CETP-expressing mice had lower circulating cholesterol concentrations than db mice. Fractionating plasma lipids by FPLC indicated that the difference in total cholesterol was primarily attributable to differences in VLDL and LDL.
Conclusions: The expression of human CETP in db/db mice prevented the formation of diet-induced lesions, suggesting an antiatherogenic effect of CETP in the context of diabetic obesity.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.