Effects of Level of Dietary Cholesterol on the Dynamic Equilibrium of Cholesterol in Rats

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Abstract
The changes in the dynamic equilibrium of cholesterol after cholesterol feeding have been studied using an isotopic balance method. Rats were fed either a purified diet (CEL) or a commercial stock diet (GP) which stimulates hepatic cholesterol biosynthesis, or were thyroidectomized (H) and fed another purified diet (A). Some rats fed each diet were also fed up to 0.5% cholesterol. After 6 months of the diet containing 0.5% cholesterol, plasma cholesterol concentrations, both free and esterified fractions, were significantly increased in all experimental conditions. The highest cholesterolemia (2.96 mg/g) was obtained in the thyroidectomized rats. In rats fed cholesterol (0.2–0.5% in the diet) cholesterol accumulation in organs was restricted to the liver, although a slight increase in carcass cholesterol content was also observed in thyroidectomized rats. The free and esterified cholesterol levels in the livers of rats fed the CEL diet without added cholesterol were respectively 1.62 and 0.37 mg/g; increased cholesterol content of the diet (0.5%) resulted in enhanced free (3.54 mg/g) and esterified (26.75 mg/g) cholesterol concentrations. Similar variations but to a lesser extent occurred in the hepatic cholesterol levels of GP rats. The absorption coefficient of cholesterol was unaffected by the amount of dietary cholesterol ingested in the CEL rats but was slightly reduced in GP and H rats. As in previous experiments, changes in cholesterol fecal excretion rates were only related to variations of the absorption coefficient except for the CEL rats fed cholesterol (0.5%) for which fecal excretion was specifically increased (7.4 mg/day instead of 4.3 mg/day for the low cholesterol CEL diet). Increases in bile acid production were well correlated with increases in cholesterol input, confirming the adaptational response of bile acid synthesis to any changes in the dynamic equilibrium of cholesterol. External fecal secretion of cholesterol, which reflects the cholesterol synthetic activity of the intestine, was not directly related to level of dietary cholesterol; the only changes could be related to variations of the absorption coefficient. The internal secretion of cholesterol which reflects cholesterol synthesized by the organs and tissues and diverted into the plasma, however, was markedly decreased in CEL rats (10.2 mg/day instead of 16.7 mg/day) and in GP rats (8.8 mg/day instead of 26.6 mg/day). Thus, cholesterol feeding suppressed cholesterol synthesis in extradigestive tissues, in particular in the liver, but did not directly affect cholesterol synthesis in the digestive tract. In thyroidectomized rats cholesterol feeding apparently did not affect internal cholesterol secretion (6.8 mg/day for low cholesterol diet, 5.3 mg/day for cholesterol-rich diet). In fact cholesterol feeding impaired the increase in the internal secretion rate related to the decreased absorption coefficient of cholesterol fed thyroidectomized rats. Moreover it is demonstrated that thyroidectomy inhibited internal secretion from both digestive and extradigestive tissues.

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