Separate pools for endogenous and exogenous cholesterol in rat intestines

Abstract

Endogenous and exogenous cholesterol were pulse labelled by intraperitoneal injection of [2- 3H]mevalonate and by gastric intubation of [4- 14C]cholesterol in rats with common bile and thoracic lymph duct fistulae. It took 3 hours for some of the exogenous cholesterol to appear in the large intestines, although a significant fraction was still present in the stomachs of the rats. The specific activity of exogenous cholesterol reached peak values and then declined at rates which were much faster than those for endogenous cholesterol in thoracic duct lymph. The free/esterified specific activity ratios for the two isotopes were different in the lymph cholesterol but they were similar for cholesterol in different segments along the length of the intestinal tract. In additional studies, cholesterol-fed rats (with cannulae in the common bile and thoracic lymph ducts) were infused intraduodenally with normal rat bile to which [4- 14C]cholesterol and [2- 3H]mevalonate had been added. The specific activity for both isotopes in the lymph cholesterol increased rapidly and stabilized by 16 hours at values many times greater than the specific activity of liver, bile, or plasma cholesterol. On removal of radioisotopes from the infusate there was an exponential decline for up to 30 hours in the specific activity of both isotopes. As in other experiments, the rate of decline for 14C was up to three times greater than that for 3H. The specific activity ratios of free/esterified cholesterol in the lymph were also consistently different for the two isotopes. These results suggest that absorption of dietary cholesterol is considerably more efficient than the absorption of endogenous cholesterol synthesized in the intestines. These data also imply that the cholesterol derived from the two sources exists in different pools in the rat intestines.