Evidence for an Intestinal Factor Stimulating Hepatic Cholesterogenesis (original) (raw)

Experimental Biology and Medicine, 1982

Abstract

Abstract External diversion of bile leads to an increase in hepatic cholesterol synthesis. To study the role of the small intestine in this phenomenon we conducted a series of experiments in bile-diverted rats with and without surgical removal of most of the small intestine, its upper half or its lower half. The pancreas was preserved intact in all experiments. Hepatic cholesterol synthesis at the time of surgery and 24 hr later was measured in liver homogenates using [2-14C]acetate as substrate. Hepatic cholesterogenesis increased almost 4-fold 24 hr after biliary diversion in rats with intact intestine, and decreased to 64% of the baseline rate in bile-diverted rats with the jejunum-ileum removed, and to 58% in sham-operated animals. To investigate the possibility that the stimulation seen in the bile-diverted rats with intact intestine was due to a substance absorbed from the diet, the experiments were repeated with animals fed only 10% glucose in water 24 hr prior to surgery. Again the rats with intact small intestine showed an increase in hepatic cholesterogenesis (6.7-fold) while those with the jejunum-ileum removed and the sham operated showed a decrease to 60 and 70% of the baseline rate, respectively. These results support the hypothesis that the small intestine produces a factor(s) that stimulates hepatic cholesterol synthesis in response to a drop in the intraluminal content of bile. To narrow the site of production of the factor(s), the effect on hepatic cholesterogenesis of removal of the upper or lower half of the small intestine in bile diverted animals was studied by comparison to a group of bile-diverted intestine-intact controls. As before, the latter showed a 6-fold increase in hepatic cholesterogenesis. With the upper or lower half of the small intestine removed a similar degree (4- to 5-fold) of stimulation was still observed. These results suggest that the factor(s) is produced along the entire length of the jejunum-ileum.

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