The cholesterolaemic effects of dietary fats in cholesteryl ester transferprotein transgenic mice

In order to investigate the role of cholesteryl ester transfer protein (CET P) in the cholesterolaemic response to dietary fats, we analysed plasma lip id 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 ac ids; 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 dietxgen otype effects on plasma total cholesterol (TC; (P<0.035 and P=0.008 respect ively), liver TC (P<0.001 and P=0.002 respectively), and esterified cholest erol (EC; P=0.002 and P=0.001 respectively); diet effects on plasma triacyl glycerol (P=0.007), liver free cholesterol (P<0.001), and body weight (P=0. 027); a genotype effect on body-weight gain (P=0.014); and a dietxgenotype effect on energy intake (P=0.006). In transgenic mice the SFA diet caused s ignificantly higher plasma TC than the PUFA diet (P<0.05). In control mice MUFA and PUFA diets, but not the SFA diet, caused significantly higher plas ma TC than the low-fat and AIN diets (P<0.05). Transgenic mice fed PUFA had lower plasma TC (P=0.040), while transgenic mice fed MUFA had lower LDL+VL DL-cholesterol (P=0.013) than controls in the same dietary groups. Transgen ic mice fed MUFA and PUFA diets also had significantly higher liver TC (P=0 .020 and P=0.002 respectively) and EC (P=0.040 and P=0.036 respectively) th an controls fed the same diets. In the present study we showed that: (1) CE TP transgenic mice had a cholesterolaemic response to dietary fats similar to that in human subjects; (2) CETP transgenic mice fed PUFA showed signifi cantly 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 apolipo protein B-containing lipoproteins and increased hepatic uptake of cholester ol, may contribute to the cholesterol-lowering effect of MUFA and PUFA in C ETP-transgenic mice; (4) CETP may play a role in appetite and/or energy reg ulation.