Deep Lipidomics and Molecular Imaging of UnsaturatedLipid Isomers: A Universal Strategy Initiated by mCPBA Epoxidation

Cellular lipidome is highly regulated through lipogenesis, rendering diverse double-bond positional isomers (C═C isomer) of a given unsaturated lipid species. In recent years, there are increasing reports indicating the physiological roles of C═C isomer compositions associated with diseases, while the biochemistry has not been broadly investigated due to the challenge in characterizing lipid isomers inherent to conventional mass spectrometry-based lipidomics. To address this challenge, we reported a universal, user-friendly, derivatization-based strategy, MELDI (mCPBA Epoxidation for Lipid Double-bond Identification), which enables both large-scale identification and spatial mapping of biological C═C isomers using commercial mass spectrometers without any instrument modification. With the developed liquid-chromatography mass spectrometry (LC-MS) lipidomics workflow, we elucidated more than 100 isomers among monounsaturated and polyunsaturated fatty acids and glycerophospholipids in human serum, where unco...