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Cited by 596

The DOI matches its Crossref record.

Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol

Yu, Liqing, Li-Hawkins, Jia, Hammer, Robert E., Berge, Knut E., Horton, Jay D., Cohen, Jonathan C., Hobbs, Helen H.·2002·Journal of Clinical Investigation
DOI 10.1172/jci0216001
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Abstract

Two ATP-binding cassette (ABC) transporters, ABCG5 and ABCG8, have been proposed to limit sterol absorption and to promote biliary sterol excretion in humans. To test this hypothesis, a P1 clone containing the human ABCG5 and ABCG8 genes was used to generate transgenic mice. The transgenes were expressed primarily in the liver and small intestine, mirroring the expression pattern of the endogenous genes. Transgene expression only modestly affected plasma and liver cholesterol levels but profoundly altered cholesterol transport. The fractional absorption of dietary cholesterol was reduced by about 50%, and biliary cholesterol levels were increased more than fivefold. Fecal neutral sterol excretion was increased three- to sixfold and hepatic cholesterol synthesis increased two- to fourfold in the transgenic mice. No significant changes in the pool size, composition, and fecal excretion of bile acids were observed in the transgenic mice. Transgene expression attenuated the increase in hepatic cholesterol content induced by consumption of a high cholesterol diet. These results demonstrate that increased expression of ABCG5 and ABCG8 selectively drives biliary neutral sterol secretion and reduces intestinal cholesterol absorption, leading to a selective increase in neutral sterol excretion and a compensatory increase in cholesterol synthesis.

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Metadata

Authors
Yu, L., Li-Hawkins, J., Hammer, R. E., Berge, K. E., Horton, J. D., Cohen, J. C., & Hobbs, H. H.
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2002-09-01
Volume
110
Issue
5
Pages
671-680
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci0216001
OpenAlex
W4247935329
Cited by
596
References
0
FWCI
44.16
Type
journal article
Language
en
Open access
closed

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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