In vivo cholesterol synthesis by the rat digestive tract. III. Evaluation of modulating factors.

Abstract

Sterol radioactivity was measured in the gastrointestinal tract of rats fed a semi-purified basal diet (B), either enriched with 0.5% cholesterol (CH) or containing 2% orotic acid (O). These measurements were taken after a fast of 48 h (CHF) or after fasting and 4-aminopyrazolopyrimidine (APP) treatment (CHFA); the five groups were killed 70 min after a subcutaneous injection of [1-14C]-acetate. Since these results agree with current published data, it is suggested that, although this method is not quantitative, it can give accurate estimates of the qualitative variations of cholesterogenesis in one organ. Adding cholesterol to the diet had no effect on sterogenesis in the stomach and caecum-colon. Fasting for 48 h did not affect cholesterogenesis in the caecum-colon, but stomacal sterogenesis was reduced (50%). APP treatment, which did not affect cholesterogenesis in the stomach, strongly stimulated (4-fold) cholesterogenesis in the caecum-colon. A slight decrease (30%) in intestinal cholesterogenesis was observed after a cholesterol-rich diet. This decrease occurred mainly in villus enterocytes. Fasting reduced cholesterol synthesis 2 to 4-fold mainly in the proximal intestine, while APP treatment stimulated it until a level higher than in nourished control rats. The level of cholesterogenesis was similar in all the enterocytes collected from duodenum to ileum in APP-treated rats. Since there was high mucosa cell loss (about 50%) during the 48-hour APP treatment, total intestinal cholesterogenesis in the CHFA rats was not higher than in the CH animals. Under the present physiological conditions, the feedback inhibition of intestinal cholesterogenesis by luminal bile acids was not clear, while that by luminal cholesterol or by LDL-cholesterol penetrating by specific receptors was modest over a wide range of physiological conditions.