Abstract
To elucidate the mechanism by which KCD-232 inhibits cholesterol absorption from intestinal lumen, we studied the influence of KCD-232 on cholesterol or fatty acid absorption, esterification of absorbed cholesterol and protein synthesis of lymph chylomicron in thoracic-duct fistura rats.
The results obtained are summaried as follows.
1) KCD-232 significantly depressed [14C] cholesterol absorption into lymph by 43.6% during the 8-hr period and by 49.5% during the 24-hr period, but did not [3H] oleic acid absorption at all.
2) KCD-232 had no effect on the distribution of absorbed [3H] oleic acid among the lipid fractions of lymph, however showed a significant decrease percentage of [14C] cholesterol associated with esterified form.
3) KCD-232 had no effect on the protein level of lymph chylomicron and [14C] leucine incorporation into chylomicron protein, and did not alter the apoprotein patterns of chylomicron as judged from polyacrylamide gel electrophorogram.
These results suggest that the inhibition of cholesterol absorption by KCD-232 may be attributed to a decrease of cholesterol esterification within mucosal cells perior to formation of chylomicron, rather than to a suppression of protein synthesis of chylomicron.
