Effect of dietary ratios of fatty acids on cholesterol metabolism in rats and on low-density lipoprotein uptake in hepatocytes

The effects of different dietary ratios of polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs) to saturated fatty acids (SFAs) [(PUFA+MUFA)/SFA] on plasma and hepatic lipids, the activities of hepatic regulatory enzymes of cholesterol metabolism, and low-density lipoprotein (LDL) uptake of hepatocytes and Kupffer cells were examined. In this study, 2 different types of diets that had the same PUFA/SFA ratio of 1.0 but each with different (PUFA+MUFA)/SFA ratios of 1.4 (diet 1, control) and 5.7 (diet 2), respectively, were fed to rats. Rats fed with diet 2 showed significantly increased plasma total triacylglycerol (TAG; 21%), very low density lipoprotein (VLDL) TAG (28%), and VLDL cholesterol (113%) levels compared with those fed with diet 1. Plasma LDL cholesterol concentration was not different between the 2 dietary groups of rats. Rats fed with diet 2 also had significantly increased hepatic cholesteryl ester concentrations (155%) and excreted less neutral sterol (35%) compared with rats in the diet 1 group. The activities of hepatic acyl coenzyme A (CoA):cholesterol acyltransferase and cholesterol 7α-hydroxylase for rats in diet group 2 were significantly increased (38% and 39%, respectively), and hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity decreased (21%) compared with the values in diet group 1. Uptake of LDL by hepatocytes (106%) and Kupffer cells (140%) was higher in rats fed with diet 2 compared with rats fed with diet 1. In summary, the diet with a high ratio (PUFA+MUFA)/SFA increased plasma total TAG, VLDL TAG, and VLDL cholesterol concentrations and liver cholesteryl ester by elevating hepatic acyl CoA:cholesterol acyltransferase and 7α-hydroxylase activities, lowering hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity, and increasing LDL uptake by hepatocytes and Kupffer cells.