Database-Driven Spatially Resolved Lipidomics Highlights Heterogeneous Metabolic Alterations in Type 2 Diabetic Mice

Spatially resolved lipidomics is pivotal for detecting
and interpreting
lipidomes within spatial contexts using the mass spectrometry imaging
(MSI) technique. However, comprehensive and efficient lipid identification
in MSI remains challenging. Herein, we introduce a high-coverage,
database-driven approach combined with air-flow-assisted desorption
electrospray ionization (AFADESI)-MSI to generate spatial lipid profiles
across whole-body mice. Using liquid chromatography coupled with tandem
mass spectrometry (LC–MS/MS), we identified 2868 unique lipids
in the serum and various organs of mice. Subsequently, we systematically
evaluated the distinct ionization properties of the lipids between
LC–MS and MSI and created a detailed MSI database containing
14 123 ions. This method enabled the visualization of aberrant
fatty acid and phospholipid metabolism across organs in a diabetic
mouse model. As a powerful extension incorporated into the MSIannotator
tool, our strategy facilitates the rapid and accurate annotation of
lipids, providing new research avenues for probing spatially resolved
heterogeneous metabolic changes in response to diseases.