What is the value of Imaging Mass Spectrometry coupled with Ion mobility to discriminate biomarkers? Study of a steatotic liver disease associated with metabolic dysfunction case

Mass spectrometry imaging -MSI- is a cutting-edge technique for visualizing the distribution of molecules within biological tissues. Matrix-Assisted Laser Desorption-Ionization -MALDI- imaging mass spectrometry is a well-established technique for the direct mapping of biomolecules in tissues. MALDI imaging coupled to ion-mobility separation dimension aids in deconvoluting these complex desorbed ion mixtures and can reveal the upregulation or downregulation of isomers. In this work, we demonstrated that MALDI quadrupole time-of-flight (Q-TOF) coupled to Trapped Ion Mobility -TIMS- spectrometry helped to visualize and discriminate biomarkers of metabolic dysfunction-associated steatotic liver disease. Sixteen liver samples from mice fed for 13 weeks chow and western diets were analyzed by untargeted MALDI-TIMS-MS to assess the changes in the liver lipidome. In this way, the TIMS-TOF fleX mass spectrometer was used with and without ion mobility dimension to visualize the lipids distribution at 50 µm spatial resolution. Major lipid identifications were performed using the Parallel Accumulation Serial Fragmentation mode (PASEF) for high-speed MS/MS analysis. Zones of interest were subsequently analyzed at higher spatial resolution (14 µm). This study demonstrates the added value of the TIMS-TOF fleX MSI analyses for lipidome investigation of hepatic liver disease, providing valuable information on the lipid zonation in liver.