Integrated proteomic and phosphoproteomic profiling unravels an O‐ <scp>GlcNAc</scp> ‐dependent mechanism in <scp>DGAT1</scp> inhibition‐mediated protection of β‐cells from lipotoxicity

Our study delineates the dynamic proteomic and phosphoproteomic landscape in Min6 cells under PA-induced lipotoxicity and its remediation by a DGAT1 inhibitor. We delineate the remodelling of key signalling pathways, changes in critical gene expression, and dysregulation of transcription factor activity that collectively contribute to PA-induced β-cell injury. Furthermore, we reveal that DGAT1 inhibition attenuates ferroptosis through a novel mechanism involving DGAT1-driven regulation of O-GlcNAcylation. This study provides new insights into DGAT1 inhibition-mediated protection against lipotoxicity and offers valuable multi-omics data resources for the research community.