Fecal steroid excretion in relation to the development of casein-induced hypercholesterolemia in rabbits

Two groups of nine rabbits fed a purified diet containing soy protein were injected intravenously with [4-14C]cholesterol. One group was fed the same diet for 78 d while the other group was fed a diet containing casein. The feces of the rabbits were collected and analyzed for radioactivity present in the neutral steroid and bile acid fractions. The excretion of neutral steroids and bile acids was lowered within 3 d after soy protein was replaced by casein and before the serum cholesterol concentration was increased. However, in the casein-fed rabbits the specific radioactivity of the bile acids was greater, whereas the amount of excreted bile acids was lower than in the soy protein-fed rabbits. After the serum cholesterol level in the casein-fed animals became constant (d 35), a further injection of [4-14C]cholesterol was given to all animals. Kinetic parameters of cholesterol metabolism according to a two-pool model were estimated from the die-away curve of [4-14C]cholesterol in serum. The size of the rapidly exchangeable pool (pool A) was greater in the casein-fed rabbits than in the soy protein-fed rabbits, whereas the size of pool B was similar in the two groups. The partial turnover rate of pool A was lower, as was the partial turnover of the slowly exchangeable pool (pool B), and the production rate of cholesterol was significantly lower on the casein-fed rabbits than in the soy protein-fed rabbits. This study suggests that the reduced excretion of steroids in casein-fed rabbits could be the cause of the hypercholesterolemia and is not the result of it.