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Published on: November 27, 2016
Ezetimibe stimulates faecal neutral sterol excretion depending on abcg8 function in mice
Lily Jakulj1, Maud N Vissers, Cindy P van Roomen
1Department of Vascular Medicine, University of Amsterdam, Amsterdam, The Netherlands. l.jakulj@amc.nl
Ezetimibe enhances fecal sterol excretion beyond cholesterol absorption inhibition. This effect requires the functional sterol exporter ATP binding cassette transporter G8 (abcg8) for non-biliary and non-dietary sterol elimination.
Area of Science:
- Biochemistry
- Pharmacology
- Molecular Biology
Background:
- Ezetimibe is known to inhibit cholesterol absorption.
- Ezetimibe also stimulates fecal neutral sterol (FNS) excretion through mechanisms not fully explained by cholesterol absorption inhibition alone.
- The sterol exporter ATP binding cassette transporter G8 (abcg8) plays a role in cholesterol transport.
Purpose of the Study:
- To investigate if the sterol exporter ATP binding cassette transporter G8 (abcg8) mediates the effects of ezetimibe on fecal sterol excretion.
- To determine the contribution of abcg8 to ezetimibe-induced 'extra' fecal sterol excretion.
Main Methods:
- Comparison of ezetimibe's effects on fecal neutral sterol (FNS) excretion in wildtype (WT) and abcg8(-/-) mice.
- Quantification of daily FNS excretion relative to dietary cholesterol intake and biliary secretion.
- Assessment of biliary cholesterol secretion in response to ezetimibe.
Main Results:
- Ezetimibe increased FNS excretion 2.7-fold in WT mice and 1.5-fold in abcg8(-/-) mice.
- Ezetimibe enhanced 'extra' FNS excretion (beyond dietary and biliary sources) by 3.5-fold in WT mice and 1.5-fold in abcg8(-/-) mice.
- These effects occurred without altering biliary cholesterol secretion, indicating a non-biliary origin.
Conclusions:
- Ezetimibe stimulates fecal sterol excretion from non-biliary and non-dietary sources, likely via trans-intestinal cholesterol excretion.
- This ezetimibe-mediated stimulation of 'extra' fecal sterol excretion is dependent on the functional integrity of the abcg8 transporter.
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