Abstract
Inhibition of glycosphingolipid synthesis with iminosugar N-(5´-adamantane-1´-yl-methoxy)-pentyl-1-deoxynojirimycin (AMP-DNM) increases fecal neutral sterol output in mice. To investigate which pathways were involved in this increase, C57Bl/6J mice were treated with AMP-DNM and/or ezetimibe. Fecal neutral sterol output increased by threefold with combined AMP-DNM/ezetimibe treatment compared with approximately twofold increases with single treatments. Bile canulations and intestine perfusions showed that biliary cholesterol secretion and transintestinal cholesterol efflux were increased in mice receiving AMP-DNM treatment. This study indicates that AMP-DNM treatment of mice increases fecal neutral sterol by promoting biliary and intestinal cholesterol secretion without inhibiting cholesterol absorption.
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