Regression of casein and cholesterol-induced hypercholesterolaemia in rabbits

Hypercholesterolaemia was induced in rabbits by feeding semipurified diets containing soy protein plus cholesterol (0.8 g/kg) or casein for four weeks. Subsequently for a period of six weeks, some of the rabbits were transferred to diets containing soy protein while others continued to receive the hypercholesterolaemic diets to which was added a mixture of amino acids (g/kg feed; glycine, 3.9; arginine, 6.9 and alanine, 1.6). Such additions increased the concentration of these amino acids in the casein diet to that in the hypocholesterolaemic soy protein diet. The cholesterol levels in the serum of the rabbits transferred to the soy protein diets declined rapidly, becoming significantly different from animals remaining on the hypercholesterolaemic diets after only three days. Serum cholesterol levels comparable to those in rabbits fed soy protein throughout the entire experiment were reached after about two weeks. The addition of the amino acids tended to reduce the concentration of cholesterol in the serum of the rabbits made hypercholesterolaemic by feeding the diets containing either casein or cholesterol. However, the effect reached significance only with the diet containing casein to which amino acids were added and then only at one time point. Six weeks after the cholesterol-fed animals were transferred to the cholesterol-free soy protein diet or to the diet containing the additional amino acids, apo E disappeared from the IDL1 (1.006 less than d less than 1.012 g/ml) and IDL2 (1.012 less than d less than 1.019 g/ml) fractions, but not from the VLDL fraction. Both with the cholesterol-free soy protein diet and the cholesterol diet fortified with amino acids, cholesterol in the VLDL fraction was reduced to values seen in animals fed the soy protein diet throughout the entire experimental period. The amount of cholesterol in the IDL and LDL fractions was decreased only in the soy protein group. Replacement of casein by soy protein, or the addition of amino acids to the casein diet did not induce the disappearance of apo E from the IDL or VLDL fractions. Only the soy protein diet lowered the amount of cholesterol in the VLDL and LDL fractions appreciably. It is concluded that the amount of apo E present in both IDL and VLDL does not invariably correlate with the level of serum cholesterol in rabbits. This study also indicates that the hypercholesterolaemic nature of casein resides only partially in the fact that it contains relatively low proportions of glycine, alanine and arginine compared with soy protein.