Cho, Joo-Youn; Matsubara, Matsubara; Kang, Dong Wook; Ahn, Sung-Hoon; Krausz, Kirstopher W; Idle, Jeffrey; Luecke, Hans; Gonzalez, Frank J (2010). Urinary metabolomics in Fxr-null mice reveals activated adaptive metabolic pathways upon bile acid challenge. Journal of lipid research, 51(5), pp. 1063-1074. Bethesda, Md.: American Society for Biochemistry and Molecular Biology ASBMB 10.1194/jlr.M002923
Full text not available from this repository.Farnesoid X receptor (FXR) is a nuclear receptor that regulates genes involved in synthesis, metabolism, and transport of bile acids and thus plays a major role in maintaining bile acid homeostasis. In this study, metabolomic responses were investigated in urine of wild-type and Fxr-null mice fed cholic acid, an FXR ligand, using ultra-performance liquid chromatography (UPLC) coupled with electrospray time-of-flight mass spectrometry (TOFMS). Multivariate data analysis between wild-type and Fxr-null mice on a cholic acid diet revealed that the most increased ions were metabolites of p-cresol (4-methylphenol), corticosterone, and cholic acid in Fxr-null mice. The structural identities of the above metabolites were confirmed by chemical synthesis and by comparing retention time (RT) and/or tandem mass fragmentation patterns of the urinary metabolites with the authentic standards. Tauro-3alpha,6,7alpha,12alpha-tetrol (3alpha,6,7alpha,12alpha-tetrahydroxy-5beta-cholestan-26-oyltaurine), one of the most increased metabolites in Fxr-null mice on a CA diet, is a marker for efficient hydroxylation of toxic bile acids possibly through induction of Cyp3a11. A cholestatic model induced by lithocholic acid revealed that enhanced expression of Cyp3a11 is the major defense mechanism to detoxify cholestatic bile acids in Fxr-null mice. These results will be useful for identification of biomarkers for cholestasis and for determination of adaptive molecular mechanisms in cholestasis.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology |
UniBE Contributor: |
Idle, Jeffrey |
ISSN: |
0022-2275 |
Publisher: |
American Society for Biochemistry and Molecular Biology ASBMB |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 14:07 |
Last Modified: |
05 Dec 2022 14:00 |
Publisher DOI: |
10.1194/jlr.M002923 |
PubMed ID: |
19965603 |
Web of Science ID: |
000276633100022 |
URI: |
https://boris.unibe.ch/id/eprint/76 (FactScience: 195176) |
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