Mechanism of Suckling Rat Hypercholesterolemia: Dietary and Drug Studies

Abstract

The objective of this study was to determine the cause(s) of the hypercholesterolemia which is known to occur in suckling rats. A semi-purified, milk-simulating diet fed to 21-day-old rats upon weaning was found to maintain the hypercholesterolemic condition. With this diet, the mechanism of suckling rat hypercholesterolemia was investigated by testing the effect of dietary levels of lactose, bulk, polyunsaturated fatty acids, cholesterol and fat. The condition appears to be dependent upon the high fat content of rat milk but independent of the dietary bulk, polyunsaturates, and carbohydrate source. Isocaloric diets were used to establish the dependency upon the fat content of diet. Feeding experiments suggest that dietary cholesterol is not necessary for maintaining hypercholesterolemia for short periods of time, but isotopic balance studies show that the dam contributes a portion of the cholesterol found in the plasma of suckling rats. Ethyl linoleate, α-p-chlorophenoxyisobutyrate (CPIB), benzmalecene, and β-diethylaminoethyl diphenylpropyl acetate hydrochloride were found not to be effective as hypocholesterolemic agents in the suckling rat hypercholesterolemia. L-Thyroxine was active in lowering plasma cholesterol in this system, but it increased liver free and total cholesterol. Liver wet weight, dry weight, and protein content increased in response to CPIB.