Back to Search Start Over

Hepatic ABCG5/G8 overexpression substantially increases biliary cholesterol secretion but does not impact in vivo macrophage-to-feces RCT.

Authors :
Dikkers A
de Boer JF
Groen AK
Tietge UJ
Source :
Atherosclerosis [Atherosclerosis] 2015 Dec; Vol. 243 (2), pp. 402-6. Date of Electronic Publication: 2015 Oct 08.
Publication Year :
2015

Abstract

Background and Aims: Biliary cholesterol secretion is important for reverse cholesterol transport (RCT). ABCG5/G8 contribute most cholesterol mass secretion into bile. We investigated the impact of hepatic ABCG5/G8 on cholesterol metabolism and RCT.<br />Methods: Biliary and fecal sterol excretion (FSE) as well as RCT were determined using wild-type controls, Abcg8 knockout mice, Abcg8 knockouts with adenovirus-mediated hepatocyte-specific Abcg8 reinstitution and hepatic Abcg5/g8 overexpression in wild-types.<br />Results: In Abcg8 knockouts, biliary cholesterol secretion was decreased by 75% (p < 0.001), while mass FSE and RCT were unchanged. Hepatic reinstitution of Abcg8 increased biliary cholesterol secretion 5-fold (p < 0.001) without changing FSE or overall RCT. Overexpression of both ABCG5/G8 elevated biliary cholesterol secretion 5-fold and doubled FSE (p < 0.001) without affecting overall RCT.<br />Conclusions: ABCG5/G8 mediate mass biliary cholesterol secretion but not from a RCT-relevant pool. Intervention strategies aiming at increasing hepatic Abcg5/g8 expression for enhancing RCT are not likely to be successful.<br /> (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1879-1484
Volume :
243
Issue :
2
Database :
MEDLINE
Journal :
Atherosclerosis
Publication Type :
Academic Journal
Accession number :
26520893
Full Text :
https://doi.org/10.1016/j.atherosclerosis.2015.10.010