Tissue cholesterol transport as modified by diet cholesterol and the nature of diet fat

Abstract

Summary Groups of rats were fed purified diets ad libitum for 10 weeks after weaning. Three diets contained no fat, 20 % safHower oil or 20 % stripped tallow respectively. Three corresponding diets contained 1 % cholesterol in addition. Five animals in each group were sacrificed at each of 1/2 periods between and 96 hours after intraperitoneal injection of [1- 14 C]-sodium acetate and gastric intubation of tritium-labeled cholesterol. Examination of the tissues led to the following conclusions: Diet cholesterol and fat each play roles in the transport of cholesterol in serum and other tissues. The roles, however, are different. Diet cholesterol decreases the concentration of high-density lipoproteins and S f 0–12 low-density lipoproteins but increases the concentration of the S f 12–20 and S f 20–400 fractions. At the same time serum cholesterol concentration increases. It is postulated that this is a result of the inhibition of cholesterol synthesis by diet cholesterol: the exogenous cholesterol transported on the low-density lipoproteins and chylomicrons replaces the endogenous, the synthesis of which may be related to high-density lipoprotein origins. Diet fat, both tallow and safflower oil, in the cholesterol-free diets increases the S f 0–12 lipoproteins. Only tallow increases the S f 20–400 fraction also. In diets containing cholesterol, tallow and safflower oil increase the S f 12–20 and Sf 20–400 fractions while tallow decreases and safflower oil increases the S f 0–12 fraction. Diet fat has no direct effect on serum cholesterol levels but enhances the responses to diet cholesterol, probably by increasing its degree of absorption. In addition, however, diet fat also decreases the time required for exogenous cholesterol to reach maximum levels in tissues, unsaturated fat being more effective than saturated. Diet fat also affects tissue cholesterol half-life, unsaturated fat reducing it and saturated fat increasing it. Low levels of tissue exogenous cholesterol radioactivities on low fat as compared to high fat diets are explained as being due to diversion of labeled acetate to fat synthesis rather than to relatively low levels of cholesterol synthesis. The aorta synthesizes cholesterol and such synthesis is not inhibited by dietary cholesterol, in contrast to the liver but similar to the intestinal mucosa.