Conflict of interest: Nothing to report.
Liver Biology and Pathobiology
Article first published online: 23 DEC 2004
Copyright © 2004 American Association for the Study of Liver Diseases
Volume 41, Issue 1, pages 141–150, January 2005
How to Cite
Kosters, A., Frijters, R. J. J. M., Kunne, C., Vink, E., Schneiders, M. S., Schaap, F. G., Nibbering, C. P., Patel, S. B. and Groen, A. K. (2005), Diosgenin-induced biliary cholesterol secretion in mice requires Abcg8. Hepatology, 41: 141–150. doi: 10.1002/hep.20540
Part of this study was presented at the 2003 American Association for the Study of Liver Diseases annual meeting and was published as an abstract in HEPATOLOGY 2003;38(Suppl 1):387A.
- Issue published online: 23 DEC 2004
- Article first published online: 23 DEC 2004
- Manuscript Accepted: 5 NOV 2004
- Manuscript Received: 14 JUL 2004
- Netherlands Organization for Scientific Research (NWO). Grant Numbers: 902-23-193, 902-23-262
- Dutch Digestive Diseases Foundation (MLDS). Grant Number: MS-00-46
- National Institutes of Health. Grant Number: NHLBI HL060613
The plant sterol diosgenin has been shown to stimulate biliary cholesterol secretion in mice without affecting the expression of the adenosine triphosphate-binding cassette transporter heterodimer Abcg5/g8. The aim of this study was to investigate the mechanism of diosgenin-induced cholesterol hypersecretion and to identify the genes involved. Surprisingly, despite its lack of effect on Abcg5/g8 expression in wild-type mice, diosgenin did not stimulate biliary cholesterol secretion in mice deficient for Abcg8. Analysis of the kinetics of cholesterol secretion suggested that diosgenin probably activates a step before Abcg5/g8. To identify potential diosgenin targets, gene expression profiling was performed in mice fed a diosgenin-supplemented diet. Diosgenin feeding increased hepatic expression of genes involved in cholesterol synthesis as well as genes encoding for several cytochrome P450s. No significant change in expression of known cholesterol transporters was found. Comparison with published expression-profiling data for Srebp2-overexpressing mice, another mouse model in which biliary cholesterol secretion is elevated, revealed a number of genes with unknown function that were upregulated in both diosgenin-fed mice and mice overexpressing Srebp2. In conclusion, we found that although Abcg8 is essential for most diosgenin-induced biliary cholesterol hypersecretion, diosgenin probably does not interact directly with Abcg5/Abcg8, but rather increases cholesterol delivery to the heterodimer. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2005;41:141–150.)