Cholesterol Metabolism in Rats Sensitive to High Cholesterol Diet

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Abstract
There was great individual variation in the elevations of serum cholesterol concentrations in a Wistar strain of rats by the ingestion of a large amount of cholesterol, although their cholesterol concentrations were almost identical while under the feeding of a regular stock diet. Their serum total phospholipid and dextran precipitable beta-lipoproteins showed the same tendencies, but serum triglyceride concentration was not affected by the dietary supplement in both groups. So, the rats with the different elevation rates of serum cholesterol concentrations were divided into good, normo and poor responding groups to cholesterol ingestion by the degrees of the elevations and bred for several generations. Serum lipid levels in the descendants from hyperresponding rats were not different from those from hyporesponding rats during the observed period, when they were given a stock diet. However, the response of serum cholesterol level to oral cholesterol ingestion in the former was larger than that in the latter. Therefore, it is suggested that the susceptibility of serum cholesterol to cholesterol ingestion may be heritable from parents to their offsprings. By the results of the tracer experiments, it was demonstrated that neither hepatic cholesterol synthesis nor absorption was affected in hyperresponding rats. On the other hand, a half life of labeled cholesterol was prolonged in this selected group. The relative fractional turnover rate was 17.8 per cent in hyporesponding rats and 15.8 per cent in hyperresponding rats. Excretion of the radioactivity from labeled cholesterol into the bile in good responding rats with bile fistula was slower than that in poor responding rats. When 1 g per 100 g body weight of glucose was given to the rats after 40 hours fasting, hepatic cholesterol synthesis increased at the same rate in both groups of rats, but the induction of hepatic cholesterol 7α-hydroxylation in hyperresponding groups was slower than that in hyporesponding groups. The distribution rates of the radioactivities into livers seemed to be delayed in good responders after the labeled cholesterol was ingested orally. It means that some disturbances in cholesterol transport may exist which induce the metabolic abnormality in such animals. It was shown that cholesterol metabolism was impaired in aged animals as compared with young ones. Serum cholesterol concentrations were elevated in good responders more than in poor responders by aging. The inborn errors of cholesterol metabolism in such animals might be emphasized from the fact of the impairment of cholesterol metabolism by the aging process.