UPLC-MS-based urine metabolomics reveals indole-3-lactic acid and phenyllactic acid as conserved biomarkers for alcohol-induced liver disease in the Ppara-null mouse model

Manna, Soumen K; Patterson, Andrew D; Yang, Qian; Krausz, Kristopher W; Idle, Jeffrey R; Fornace, Albert J; Gonzalez, Frank J (2011). UPLC-MS-based urine metabolomics reveals indole-3-lactic acid and phenyllactic acid as conserved biomarkers for alcohol-induced liver disease in the Ppara-null mouse model. Journal of proteome research, 10(9), pp. 4120-33. Washington, D.C.: American Chemical Society 10.1021/pr200310s

Full text not available from this repository. (Request a copy)

Since the development and prognosis of alcohol-induced liver disease (ALD) vary significantly with genetic background, identification of a genetic background-independent noninvasive ALD biomarker would significantly improve screening and diagnosis. This study explored the effect of genetic background on the ALD-associated urinary metabolome using the Ppara-null mouse model on two different backgrounds, C57BL/6 (B6) and 129/SvJ (129S), along with their wild-type counterparts. Reversed-phase gradient UPLC-ESI-QTOF-MS analysis revealed that urinary excretion of a number of metabolites, such as ethylsulfate, 4-hydroxyphenylacetic acid, 4-hydroxyphenylacetic acid sulfate, adipic acid, pimelic acid, xanthurenic acid, and taurine, were background-dependent. Elevation of ethyl-β-d-glucuronide and N-acetylglycine was found to be a common signature of the metabolomic response to alcohol exposure in wild-type as well as in Ppara-null mice of both strains. However, increased excretion of indole-3-lactic acid and phenyllactic acid was found to be a conserved feature exclusively associated with the alcohol-treated Ppara-null mouse on both backgrounds that develop liver pathologies similar to the early stages of human ALD. These markers reflected the biochemical events associated with early stages of ALD pathogenesis. The results suggest that indole-3-lactic acid and phenyllactic acid are potential candidates for conserved and pathology-specific high-throughput noninvasive biomarkers for early stages of ALD.

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:

1535-3893

Publisher:

American Chemical Society

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:22

Last Modified:

17 Mar 2015 21:01

Publisher DOI:

10.1021/pr200310s

PubMed ID:

21749142

Web of Science ID:

000294446600023

URI:

https://boris.unibe.ch/id/eprint/7736 (FactScience: 213062)

Actions (login required)

Edit item Edit item
Provide Feedback