期刊
CELL METABOLISM
卷 24, 期 6, 页码 783-794出版社
CELL PRESS
DOI: 10.1016/j.cmet.2016.10.001
关键词
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资金
- Netherlands Heart Foundation
- Netherlands Foundation for Cardiovascular Excellence
- Netherlands CardioVascular Research Initiative (the Dutch Heart Foundation) [CVON2011-19]
- Netherlands CardioVascular Research Initiative (Dutch Federation of University Medical Centres) [CVON2011-19]
- Netherlands CardioVascular Research Initiative (Netherlands Organisation for Health Research and Development) [CVON2011-19]
- Netherlands CardioVascular Research Initiative (Royal Netherlands Academy of Sciences) [CVON2011-19]
- European Commission [FP7-305707]
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.
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