Oxygen attachment dissociation (OAD) MS/MS in the identification of positional isomers of dysregulated lipids detected in an ethanol exposure metabolomics study in mice
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Introduction
In metabolic profiling studies the structural characterisation of lipids requires the identification of the head group, carbon number and the position(s) of carbon-carbon double bonds (C = C). Locating the position of double bonds is vital since minor structural differences between positional isomers can alter a lipid’s biochemical function.
Objectives
Oxygen Attachment Dissociation (OAD) is a novel fragmentation technology that enables the localisation of C = C double bonds in lipids. To evaluate its use in the structural characterisation of lipids, OAD has been applied in a discovery-based untargeted analysis of the metabolic impact of acute ethanol exposure in a mouse model.
Methods
UHPLC-OAD-MS/MS was used to enhance the identification of lipids found to be significantly altered by acute ethanol exposure in the gut, liver and pancreas tissues of male C57BL/6 mice receiving a Lieber-DeCarli liquid diet either containing 5% ethanol or an isocaloric control diet. Tissue extracts were analysed using untargeted UHPLC-DIA-MS/MS; UHPLC-OAD-MS/MS analysis was performed to further annotate lipids that were significantly increased or diminished in the animals exposed to ethanol.
Results
UHPLC-DIA-MS/MS analysis of gut, liver and pancreas tissue revealed 101 lipids that were significantly increased or diminished in ethanol treated mice. Of the included 83 unsaturated lipids detected, UHPLC-OAD-MS/MS enabled the localisation of C = C double bonds in 61, including isomers indistinguishable by MS/MS with collision induced dissociation.
Conclusions
The results demonstrate the value of OAD-MS/MS in enhancing lipid identification. The resulting improvement may enable better understanding of the underlying biochemistry in the response of mice to exposure to ethanol.
In metabolic profiling studies the structural characterisation of lipids requires the identification of the head group, carbon number and the position(s) of carbon-carbon double bonds (C = C). Locating the position of double bonds is vital since minor structural differences between positional isomers can alter a lipid’s biochemical function.
Objectives
Oxygen Attachment Dissociation (OAD) is a novel fragmentation technology that enables the localisation of C = C double bonds in lipids. To evaluate its use in the structural characterisation of lipids, OAD has been applied in a discovery-based untargeted analysis of the metabolic impact of acute ethanol exposure in a mouse model.
Methods
UHPLC-OAD-MS/MS was used to enhance the identification of lipids found to be significantly altered by acute ethanol exposure in the gut, liver and pancreas tissues of male C57BL/6 mice receiving a Lieber-DeCarli liquid diet either containing 5% ethanol or an isocaloric control diet. Tissue extracts were analysed using untargeted UHPLC-DIA-MS/MS; UHPLC-OAD-MS/MS analysis was performed to further annotate lipids that were significantly increased or diminished in the animals exposed to ethanol.
Results
UHPLC-DIA-MS/MS analysis of gut, liver and pancreas tissue revealed 101 lipids that were significantly increased or diminished in ethanol treated mice. Of the included 83 unsaturated lipids detected, UHPLC-OAD-MS/MS enabled the localisation of C = C double bonds in 61, including isomers indistinguishable by MS/MS with collision induced dissociation.
Conclusions
The results demonstrate the value of OAD-MS/MS in enhancing lipid identification. The resulting improvement may enable better understanding of the underlying biochemistry in the response of mice to exposure to ethanol.
Date Issued
2025-07-01
Date Acceptance
2025-06-04
Citation
Metabolomics, 2025, 21 (4)
ISSN
1573-3882
Publisher
Springer
Start Page
95
Journal / Book Title
Metabolomics
Volume
21
Issue
4
Copyright Statement
© The Author(s) 2025 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
10.1007/s11306-025-02282-8
Subjects
Liver
Pancreas
Animals
Mice, Inbred C57BL
Mice
Oxygen
Ethanol
Lipids
Chromatography, High Pressure Liquid
Isomerism
Male
Lipid Metabolism
Tandem Mass Spectrometry
Metabolomics
Publication Status
Published
Article Number
95
Date Publish Online
2025-07-01