Lipid Mass Tags via Aziridination for Probing Unsaturated Lipid Isomers and Accurate Relative Quantification

Area of Science:

• Lipidomics
• Biochemistry
• Analytical Chemistry

Background:

• Accurate lipid quantification is crucial for understanding physiological roles and identifying disease biomarkers.
• Lipid analysis is challenging due to diverse structures and numerous isomeric forms.
• Existing methods struggle with precise quantification of unsaturated lipids and nonpolar lipid ionization.

Purpose of the Study:

• To develop a novel aziridine-based isobaric tag labeling strategy for lipid analysis.
• To enable determination of lipid double-bond positional isomers.
• To improve relative quantification of unsaturated lipids and ionization efficiency of nonpolar lipids.

Main Methods:

• Development of a novel aziridine-based isobaric tag labeling strategy.
• Application of the method for characterization and quantification of fatty acids, phosphoglycerol lipids, cholesteryl esters (CE), and glycerides.
• Simultaneous identification and quantification of 17 CE lipid isomers from Alzheimer's disease (AD) mouse serum without standards.

Main Results:

• The novel method accurately quantifies unsaturated lipids and enhances ionization of nonpolar lipids.
• Successfully determined lipid double-bond positional isomers.
• Identified and quantified 17 CE isomers in AD mouse serum, with 6 isomers showing significant concentration changes.

Conclusions:

• The aziridine-based labeling strategy offers a powerful tool for comprehensive lipid profiling.
• This method advances the accurate quantification of complex lipid mixtures, including isomers.
• The findings provide insights into lipid alterations in Alzheimer's disease.