Cholesterol synthesis in bypassed segments of the small intestine in hyperphagic rats.

Previous studies have demonstrated that a variety of conditions that result in an increase in food intake lead to an increase in small-intestinal cholesterol synthesis. In the present study, it was determined whether hyperphagia induces an increase in cholesterol synthesis in segments of the small intestine excluded from contact with the food stream and whether this increase would occur in bypassed segments of the proximal or mid-small intestine. In hyperphagic diabetic rats, cholesterol synthesis is increased 91% in the proximal portion of the small intestine excluded from contact with nutrients. In lactating rats, another model of hyperphagia, cholesterol synthesis is increased 2.4-fold in midintestinal segments excluded from contact with the food stream and 2.9-fold in segments of the proximal intestine that have been bypassed. These observations demonstrate that the hyperphagia-induced increase in small-intestinal cholesterol synthesis will occur in portions of the small intestine, even if contact with the food stream is prevented. In addition, this data demonstrated that the mass of the bypassed portion of the small intestine is increased in hyperphagic animals. In diabetic animals, the weight of the bypassed proximal intestine is increased 2.1-fold, whereas in lactating animals the mass is increased 50% in the bypassed midintestine and 74% in the bypassed proximal small intestine. In conclusion, the present study suggests that circulating or neurologic factors, or both, play a role in stimulating intestinal cholesterol synthesis in hyperphagic animals. These findings also suggest that indirect factors play a role in the increase in intestinal mass associated with hyperphagia.