Homeostasis of mucosal cholesterol in the small intestine of the rat

Abstract

This study was undertaken to investigate the capacity of the intestinal mucosa to maintain a constant cholesterol content under conditions where mucosal uptake or cholesterol transport into the lymph were manipulated. Two series of bile-diverted unanaesthetised rats were infused intraduodenally with saline, triolein emulsified with Pluronic F68, or taurocholate with or without added tomatine. Pluronic F68 is a nontoxic detergent which promotes mucosal uptake of polar lipids but not cholesterol. Tomatine is a cholesterol-binding saponin. One series of rats was used for measuring mucosal cholesterol content, DNA and protein after the test infusions. A second series of rats had the thoracic lymph duct cannulated but otherwise remained the same as the first series. The second series was used for measuring the effect of the different infusions on mass cholesterol output into lymph. Mucosal cholesterol content of rats that were not fed decreased with bile-diversion and was restored with taurocholate infusion. This suggested a contribution of luminal cholesterol to the mucosal cholesterol pool. However, evidence for a contribution from the lumen was provided by only one of two groups of rats given infusions which did not promote mucosal uptake of cholesterol. First, addition of tomatine to the taurocholate infusate prevented both the increase in lymph output of cholesterol and the increased mucosal cholesterol content shown in rats given taurocholate alone. Second, in another group of rats in which mucosal uptake of cholesterol was prevented, i.e. in rats given Pluronic F68-triolein emulsions, the increased fat absorption was accompanied by a marked increase in cholesterol output into lymph without a concomitant decrease in mucosal cholesterol content. These results would be consistent with increased mucosal synthesis of cholesterol as a possible source of endogenous cholesterol absorbed into lymph.