Signatures of Proteomics and Glycoproteomics Reveal Liraglutide Ameliorates NAFLD by Regulating Specific Metabolic Homeostasis in Mice

Liraglutide, a GLP-1 receptor agonist approved for diabetes and obesity, shows promise in treating NAFLD, the most prevalent chronic liver disease globally. Despite its therapeutic potential, the systematic molecular regulations underlying Liraglutide effects on NAFLD remain underexplored, indicating the crucial need to fully understand its mechanism and facilitate its use in NAFLD treatment.Based on this,we established NAFLD modele by feeding C57/BL6 mice a high-fat diet (HFD). After administration of liraglutide injection to HFD mice, liver biochemical parameters were measured to assess the efficacy of liraglutide. Mouse livers were extracted for label-free quantitative proteomics and glycoproteomics analysis to summarize the mechanism of action of liraglutide in ameliorating NAFLD. Meanwhile, liraglutide hydrogels were prepared and characterized to extend the interval of liraglutide injection administration. Our research showed that liraglutide therapeutic effect on NAFLD was largely driven by significant glycosylation changes, which have a more profound impact than changes in overall protein expression. These insights into Liraglutide regulatory networks and targets offered valuable guidance for optimizing NAFLD treatment and advancing its clinical application.