HDL biology
CETP transgenic mice reproduce the human-like cholesterol response to dietary fat type, with MUFA and PUFA lowering plasma cholesterol (Br J Nutr 2001)
Original title: The cholesterolaemic effects of dietary fats in cholesteryl ester transfer protein transgenic mice
CETP-transgenic and control C57BL/6 mice were fed standard chow, a low-fat diet, or diets high in saturated (butter), monounsaturated (high-oleic safflower oil), or polyunsaturated (safflower oil) fat for five weeks. Diet and diet-by-genotype interactions significantly affected plasma and liver total and esterified cholesterol. In transgenic mice, the saturated-fat diet produced significantly higher plasma cholesterol than the polyunsaturated-fat diet, whereas in controls, monounsaturated and polyunsaturated diets, but not saturated fat, raised cholesterol above low-fat and chow levels. Transgenic mice on polyunsaturated fat had lower plasma total cholesterol, and those on monounsaturated fat had lower LDL+VLDL-cholesterol, than controls on the same diets, though both groups had higher liver cholesterol than controls. The authors conclude CETP-transgenic mice reproduce a human-like cholesterolemic response to dietary fat type, with hepatic cholesterol accumulation possibly explaining the cholesterol-lowering effect of monounsaturated and polyunsaturated fat in these mice, and suggest CETP may also influence appetite or energy regulation.
Original abstract
In order to investigate the role of cholesteryl ester transfer protein (CETP) in the cholesterolaemic response to dietary fats, we analysed plasma lipid profiles of CETP-transgenic and control C57BL/6 mice fed standard chow (AIN-93G; AIN), a low-fat diet, and diets high in butter (saturated fatty acids; SFA), high-oleic acid safflower oil (monounsaturated fatty acids; MUFA), and safflower oil (polyunsaturated fatty acids; PUFA) for 5 weeks. Each group contained four or five mice. There were significant diet and dietxgenotype effects on plasma total cholesterol (TC; and respectively), liver TC ( and respectively), and esterified cholesterol (EC; and respectively); diet effects on plasma triacylglycerol liver free cholesterol and body weight a genotype effect on body-weight gain and a dietxgenotype effect on energy intake In transgenic mice the SFA diet caused significantly higher plasma TC than the PUFA diet In control mice MUFA and PUFA diets, but not the SFA diet, caused significantly higher plasma TC than the low-fat and AIN diets Transgenic mice fed PUFA had lower plasma TC while transgenic mice fed MUFA had lower LDL+VLDL-cholesterol than controls in the same dietary groups. Transgenic mice fed MUFA and PUFA diets also had significantly higher liver TC and respectively) and EC and respectively) than controls fed the same diets. In the present study we showed that: (1) CETP transgenic mice had a cholesterolaemic response to dietary fats similar to that in human subjects; (2) CETP transgenic mice fed PUFA showed significantly lower plasma TC, while those fed MUFA had lower LDL+VLDL-cholesterol than controls; (3) hepatic accumulation of cholesterol, possibly resulting from the combination of the enhanced cholesteryl ester transfer to apolipoprotein B-containing lipoproteins and increased hepatic uptake of cholesterol, may contribute to the cholesterol-lowering effect of MUFA and PUFA in CETP-transgenic mice; (4) CETP may play a role in appetite and/or energy regulation.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.