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

Knowing concentrations of lipids is essential for understanding their physiological functions and discovering new disease biomarkers. However, it is highly challenging to accurately quantify lipids due to structural diversity and multiple isomeric forms of lipids. To address these critical gaps, we have developed a novel aziridine-based isobaric tag labelling strategy that allows (i) determination of lipid double-bond positional isomers, (ii) accurate relative quantification of unsaturated lipids, and (iii) improvement of ionization efficiencies of nonpolar lipids. The power of this method is demonstrated in characterization and quantification of various categories of lipids such as fatty acids, phosphoglycerol lipids, cholesteryl esters (CE), and glycerides. 17 CE lipid isomers were identified and quantified simultaneously from Alzheimer's disease (AD) mouse serum without using lipid standards. Among them, 6 CE isomers showed significant changes in concentrations in AD serum.

Automated summary

Accurate measurement of lipid concentrations is crucial for understanding their functions and identifying disease biomarkers. A novel isobaric tag labelling strategy has been developed to address the challenges in lipid quantification, allowing determination of lipid isomers, relative quantification of unsaturated lipids, and improved ionization efficiencies of nonpolar lipids. This method has been successfully applied to characterize and quantify various types of lipids, including CE lipids in Alzheimer's disease serum.