Effect of dietary lecithin on cholesterol esterification, tissue cholesterol and platelet aggregation in guinea pigs

approved by: Elisabeth S. Yearick Adult male guinea pigs were maintained on four dietary regimens for a period of 8 weeks. The basic diet consisted of powdered guinea pig chow with 10% coconut oil. The three experimental groups received the basic diet with additions of either 1% lecithin, 0.25% cholesterol, or 0.25% cholesterol plus 1% lecithin. Blood was sampled periodically for the determination of plasma cholesterol, phospholipids, lecithin:cholesterol acy1transferase activity (LCAT), and platelet aggregation. Animals were sacrificed at eight weeks and the concentrations of cholesterol in selected tissues and in the carcass were determined. The cholesterol-fed animals gained less weight than did the controls; this was associated with reduced food consumption and also decreased feed efficiency. The plasma lipids responded to cholesterol feeding with a sharp increase in total cholesterol, free cholesterol, total phospholipids, phosphatidyl choline (PC), and lysophosphatidyl choline (LPC). The ratio of cholesterol:phospholipid increased, whereas the ratios of cholesterol ester:total cholesterol, LPC:total phospholipid, and LPC:PC declined. The reduced percentage of cholesterol ester and LPC suggested a limited ability to esterify the high levels of circulating cholesterol that accompanied cholesterol feeding. Although the net esterification (micromoles of cholesterol esterified) by LCAT increased with cholesterol treatment, the percent of plasma cholesterol esterified (fractional esterification) declined. Addition of lecithin to the cholesterol diet did not prevent the sharp rise in plasma cholesterol, phospholipids, or their fractions. The net esterification increased in plasma of animals receiving lecithin plus cholesterol. Nevertheless, the increase in LCAT activity was insufficient to maintain the proportion of esterified cholesterol at the level found in control animals. There was an increase in total phospholipid, PC, and LPC in plasma of guinea pigs supplemented with lecithin only; no change in cholesterol or cholesterol ester of plasma was seen. The molar esterification rate was positively correlated with plasma concentrations of both the substrates (free cholesterol and PC) and the products (cholesterol ester and LPC) of LCAT action. There was a strong positive correlation between the fractional esterification rate and the percent of esterified cholesterol, percent of LPC, and the ratio of LPC:PC. Cholesterol treatment produced an increase in the relative sizes of spleen and liver, and definitely increased the cholesterol deposition in the total body as well as selected tissues (spleen, liver, kidney, lungs, digestive tract). The increased deposition in the liver as well as total body was even greater when licithin was included in the atherogenic diet. Sudan staining of thoracic aorta revealed plaques especially around the aortic arch of animals receiving cholesterol only; the addition of lecithin to the atherogenic diet resulted in a reduced number of plaques. ADP-induced platelet aggregation was enhanced with cholesterol feeding. The sensitivity of platelets to ADP aggregation was reduced in animals treated with lecithin plus cholesterol. The correspondence of platelet aggregation to the prevalence of aortic plaques suggests that contact with damaged vascular walls may have altered platelet sensitivity. Positive correlations existed between platelet aggregation and plasma concentrations of free and esterified cholesterol as wel1 as PC and LPC. The overall results suggest that the increase in the rate of cholesterol esterification and the decrease in the platelet sensitivity may be the mechanism by which lecithin reduces the incidence and severity of atherosclerosis. EFFECT OF DIETARY LECITHIN ON CHOLESTEROL ESTER IFlCATION, TISSUE CHOLESTEROL AND PLATELET AGGREGATION IN GUINEA PIGS by Gil-Won Song Cusack A THESIS submi tted to Oregon State University in partial fulfiIIment of the requirement for the degree of Doctor of Philosophy Commencement June 1978