Mitochondrial viscosity, oxidative stress and autophagy responsive fluorescent Zn(II) complex for monitoring non-alcoholic fatty liver disease

Accumulating evidence highlights the critical role of dysfunctional mitochondrial quality control in the pathogenesis of non–alcoholic fatty liver disease (NAFLD). However, there is limited information available regarding of viscosity–related cellular metabolic processes of NAFLD. To address this, we developed a novel viscosity–sensitive fluorescent metal Zn(II) complex, LIFM–ZY–1, for monitoring viscosity changes with one–photon (OP) and two–photon (TP) fluorescence. It could effectively track cellular oxidative stress induced by lipotoxicity with viscosity changes, as reflected by viscosity changes in the OP/TP channel. Besides, LIFM–ZY–1 was capable of detecting non–selective mitophagy triggered by starvation in real time and selective mitophagy induced by autophagy drug rapamycin. Moreover, LIFM–ZY–1 successfully monitored the deterioration and therapeutic outcome of NAFLD mice with changing viscosity induced by overeating and autophagy drug empagliflozin. Overall, our findings demonstrated the potential of LIFM–ZY–1 as a valuable tool for real time monitoring NAFLD treatment through viscosity, oxidative stress and autophagy changes, offering valuable insights into the underlying biological processes and potential therapeutic strategies for NAFLD.