title: Ezetimibe stimulates faecal neutral sterol excretion depending on abcg8 function in mice.
abstract: Ezetimibe stimulates faecal neutral sterol (FNS) excretion in mice, which cannot be explained by cholesterol absorption inhibition alone. We investigated whether these effects are mediated via the sterol exporter ATP binding cassette transporter G8 (abcg8). Ezetimibe increased FNS excretion 2.7-fold in WT mice and 1.5-fold in abcg8(-/-) mice, without affecting biliary cholesterol secretion. Daily FNS excretion exceeded the sum of dietary cholesterol intake and biliary secretion by about 60%. Ezetimibe enhanced this 'extra' FNS excretion by 3.5-fold and 1.5-fold in wildtype (WT) and abcg8(-/-) mice, respectively. Ezetimibe stimulates fecal sterol excretion of non-biliary and non-dietary origin, probably through stimulation of trans-intestinal cholesterol excretion. We show that this effect depends on intact abcg8 function.
authors.affiliation: Department of Vascular Medicine, University of Amsterdam, Amsterdam, The Netherlands. l.jakulj@amc.nl
authors.forename: Lily
authors.initials: L
authors.lastname: Jakulj
authors.forename: Maud N
authors.initials: MN
authors.lastname: Vissers
authors.forename: Cindy P
authors.initials: CP
authors.lastname: van Roomen
authors.forename: Jelske N
authors.initials: JN
authors.lastname: van der Veen
authors.forename: Carlos L J
authors.initials: CL
authors.lastname: Vrins
authors.forename: Cindy
authors.initials: C
authors.lastname: Kunne
authors.forename: Frans
authors.initials: F
authors.lastname: Stellaard
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Albert K
authors.initials: AK
authors.lastname: Groen
mesh_terms: D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001384:Azetidines / Q000494:pharmacology*; D001646:Bile / Q000378:metabolism; D001693:Biological Transport, Active / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D000069438:Ezetimibe; D005243:Feces / Q000737:chemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008074:Lipoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013261:Sterols / Q000378:metabolism*
chemical_list: C462601:ABCG8 protein, mouse; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D001384:Azetidines; D008074:Lipoproteins; D013261:Sterols; D002784:Cholesterol; D000069438:Ezetimibe