Deep Lipidomics and Molecular Imaging of Unsaturated Lipid Isomers: A Universal Strategy Initiated by mCPBA Epoxidation
Cellular lipidome is highly regulated through lipogenesis, rendering diverse double-bond positional isomers (CC isomer) of a given unsaturated lipid species. In recent years, there are increasing reports indicating the physiological roles of CC isomer compositions associated with diseases, while t...
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Published in | Analytical chemistry (Washington) Vol. 91; no. 18; pp. 11905 - 11915 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Chemical Society
17.09.2019
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Subjects | |
Online Access | Get full text |
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Summary: | Cellular lipidome is highly regulated through lipogenesis, rendering diverse double-bond positional isomers (CC isomer) of a given unsaturated lipid species. In recent years, there are increasing reports indicating the physiological roles of CC 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 CC 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 uncommon isomers of low abundance were quantified for the first time. The capability of MELDI-LC-MS in lipidome analysis was further demonstrated using the differentiated 3T3-L1 adipocytes, providing an insight into the cellular lipid reprogramming upon stearoyl-coenzyme A desaturase 1 (SCD1) inhibition. Finally, we highlighted the versatility of MELDI coupled with ambient mass spectrometry imaging to spatially resolve cancer-associated alteration of lipid isomers in a metastatic mouse tissue section. Our results suggested that MELDI will contribute to current lipidomics pipelines with a deeper level of structural information, allowing us to investigate the underlying lipid biochemistry. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0003-2700 1520-6882 |
DOI: | 10.1021/acs.analchem.9b02667 |