Cholesterol and bile-acid metabolism in normal and cholesterol-fed rabbits after partial lleal bypass

Abstract

The effects of partial ileal bypass on plasma lipids, tissue cholesterol biosynthesis, and liver 7α-hydroxylation were studied in rabbits on a normal diet and after cholesterol feeding. The surgical procedure was minimally effective in control animals, whereas it dramatically reduced (even below baseline) plasma cholesterol levels in the diet-treated group. Liver cholesterol biosynthesis from [ 14C]acetate was not detectable in control rabbits. In these, biosynthesis from [ 14C]mevalonate was revealed in the liver and intestine, particularly in the duodenum. Cholesterol feeding totally suppressed the intestinal and liver biosynthetic activity, both from [ 14C]acetate and [ 14C]mevalonate. Partial ileal bypass significantly raised liver cholesterol biosynthesis from [ 14C]mevalonate, particularly in animals on the hyper-cholesterolemic regimen. No cholesterol 7α-hydroxylase activity, as determined by a mass fragmentographic technique, was found in control and cholesterol-fed rabbits; after partial ileal bypass, activities of 167 and 643 pmol·mg protein −1·hr −1, respectively, were found in controls and hypercholesterolemic animals. These findings underline the sensitivity of rabbits both to cholesterol feeding and to partial ileal bypass, a condition possibly related to the very low sterol synthetic activity in these animals. They also suggest that the surgical procedure may alter some regulatory step in tissue cholesterol biosynthesis.