|Abstract or Summary
- 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
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 lecithin 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.