Abstract
ObjectiveMetabolomics is a promising approach to the identification of biomarkers in plasma. Here, we performed a population-based, cross-sectional study to identify potential biomarkers of alcohol intake and alcohol-induced liver injury by metabolomic profiling using capillary electrophoresis-mass spectrometry (CE-MS).MethodsFasting plasma samples were collected from 896 Japanese men who participated in the baseline survey of the Tsuruoka Metabolomics Cohort Study, and 115 polar metabolites were identified and absolutely quantified by CE-MS. Information on daily ethanol intake was collected through a standardized, self-administered questionnaire. The associations between ethanol intake and plasma concentration of metabolites were examined. Relationships between metabolite concentrations or their ratios and serum liver enzyme levels in the highest ethanol intake group (>46.0 g/day) were then examined by linear regression analysis. Replication analysis was conducted in 193 samples collected from independent population of this cohort.ResultsNineteen metabolites were identified to have an association with daily alcohol consumption both in the original and replication population. Three of these metabolites (threonine, glutamine, and guanidinosuccinate) were found to associate well with elevated levels of serum liver enzymes in the highest ethanol intake group, but not in the non-drinker group. We also found that the glutamate/glutamine ratio had a much stronger relation to serum γ-glutamyltransferase, aspartate transaminase, and alanine transaminase than glutamate or glutamine alone (standardized beta = 0.678, 0.558, 0.498, respectively).ConclusionsWe found 19 metabolites associated with alcohol intake, and three biomarker candidates (threonine, guanidinosuccinate and glutamine) of alcohol-induced liver injury. Glutamate/glutamine ratio might also be good biomarker.Electronic supplementary materialThe online version of this article (doi:10.1007/s12199-015-0494-y) contains supplementary material, which is available to authorized users.
Highlights
We found 19 metabolites associated with alcohol intake, and three biomarker candidates of alcohol-induced liver injury
C-GTP and aspartate transaminase (AST) levels were elevated with increasing alcohol intake, as were systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein (HDL)-cholesterol, and the percentage of participants with high daily physical activity, while LDLcholesterol and the percentage of participants with high dietary energy intake decreased with increasing alcohol intake
We revealed the metabolomic differences induced by alcohol intake and found new biomarker candidates of alcohol-induced liver injury in human plasma using capillary electrophoresis-mass spectrometry (CE-MS)-based global metabolomic profiling among community-dwelling men
Summary
Eight metabolites were associated with serum c-GTP in the original set, and six metabolites’ [threonine, guanidinosuccinate, glutamine, choline, carnitine, and cysteine-glutathione disulfide (CSSG)] associations were observed in the replication set These results remained mostly unchanged even after adjustment for possible confounders. Threonine had negative associations with serum c-GTP and AST levels among non-drinkers but positive associations in the high-intake group These observations were found in the replication set. Guanidinosuccinate, glutamine, and choline which showed associations (FDR p \ 0.05) in the high-intake group had no association in the non-drinkers In contrast to these metabolites, CSSG had strong associations with serum liver enzymes in both the non-drinker and high-intake groups, indicating that the observed associations were likely due to factors other than alcohol intake. These results were consistent even after excluding ex-drinkers from non-drinkers
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
