Transintestinal Cholesterol Transport Is Active in Mice and Humans and Controls Ezetimibe-Induced Fecal Neutral Sterol Excretion

Lily Jakulj, Theo H. van DIjk, Jan Freark de Boer, Ruud S Kootte, Marleen Schonewille, Yared Paalvast, Theo Boer, Vincent W Bloks, Renze Boverhof, Max Nieuwdorp, Ulrich H W Beuers, Erik S G Stroes, Albert K Groen

OnderzoeksoutputAcademicpeer review

71 Citaten (Scopus)
134 Downloads (Pure)

Samenvatting

Except for conversion to bile salts, there is no major cholesterol degradation pathway in mammals. Efficient excretion from the body is therefore a crucial element in cholesterol homeostasis. Yet, the existence and importance of cholesterol degradation pathways in humans is a matter of debate. We quantified cholesterol fluxes in 15 male volunteers using a cholesterol balance approach. Ten participants repeated the protocol after 4 weeks of treatment with ezetimibe, an inhibitor of intestinal and biliary cholesterol absorption. Under basal conditions, about 65% of daily fecal neutral sterol excretion was bile derived, with the remainder being contributed by direct transintestinal cholesterol excretion (TICE). Surprisingly, ezetimibe induced a 4-fold increase in cholesterol elimination via TICE. Mouse studies revealed that most of ezetimibe-induced TICE flux is mediated by the cholesterol transporter Abcg5/Abcg8. In conclusion, TICE is active in humans and may serve as a novel target to stimulate cholesterol elimination in patients at risk for cardiovascular disease.

Originele taal-2English
Pagina's (van-tot)783-794
Aantal pagina's12
TijdschriftCell metabolism
Volume24
Nummer van het tijdschrift6
DOI's
StatusPublished - 13-dec-2016

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