Spatiotemporal Super‐Resolution Imaging of Lipid Metabolism Dynamics in Physiological/Pathological Conditions

Dysregulated lipid metabolism plays a critical role in the pathogenesis of numerous diseases. However, due to the lack of effective solutions, the dynamic monitoring and deep understanding of lipid metabolism in those disease progression has remained challenging. Herein, a polarity-sensitive, lipid droplets (LDs)-targeted probe was developed for spatiotemporal super-resolution imaging of lipid metabolism dynamics. Based on the stimulated emission depletion (STED) and fluorescence lifetime imaging microscopy (FLIM) platform, we achieved the super-resolution visualization and dynamic tracking of the nonlinear fusion and expansion mechanisms of LDs in orthotopic pathology models-an unprecedented achievement in the field. We also analyzed lipid distribution in zebrafish models using the STED-FLIM platform to capture lipid metabolism at the organismal level. Crucially, based on the integrated STED-FLIM platform, this probe accurately monitors lipid metabolism in cellular and pathological tissue contexts of atherosclerosis and fatty liver. This breakthrough provides novel insights for diagnosing lipid metabolism-related diseases and advancing therapeutic development.