Multimodal mass spectrometry imaging reveals spatial metabolic reprogramming in diabetic liver disease

Diabetic liver injury (DLI) is a significant complication of diabetes mellitus, leading to severe liver dysfunction and non-alcoholic fatty liver disease (NAFLD). Understanding the metabolic alterations and reprogramming in DLI is critical for identifying therapeutic targets. Despite the prevalence of DLI, its underlying metabolic mechanisms remain poorly understood, and effective treatments are lacking. In this study, we employed a multimodal mass spectrometry imaging approach, combining air-flow-assisted desorption electrospray ionization (AFADESI-MSI) with matrix-assisted laser desorption ionization (MALDI-MSI) to achieve a comprehensive spatial analysis of metabolic changes in DLI model rats, focusing on the potential therapeutic effects of ferulic acid, a compound known for its antioxidant and anti-inflammatory properties. This approach allowed for the wide-coverage and high-resolution visualization of over 200 metabolites in the liver tissues of DLI model rats. The study involved comparing metabolic profiles between control, DLI, and ferulic acid-treated groups, with ferulic acid administered at a dosage of 50 mg/kg daily for 20 weeks. The analysis revealed significant metabolic reprogramming in DLI, characterized by alterations in glucose, lipid, bile acid, and nucleotide metabolism. Specifically, we identified over 100 metabolites with heterogeneous distributions across liver sections, highlighting region-specific metabolic impairments. Ferulic acid treatment notably reversed many of these metabolic disturbances, particularly in glucose and lipid metabolism, suggesting its potential to restore metabolic homeostasis in DLI. This study provides critical insights into the metabolic underpinnings of DLI and demonstrates the therapeutic potential of ferulic acid in modulating these pathways. The findings underscore the utility of AFADESI- and MALDI-MSI in studying liver diseases and suggest that the metabolites identified could serve as novel biomarkers for DLI diagnosis and treatment.