miR-20a-5p targeting mfn2-mediated mitochondria-lipid droplet contacts regulated differential changes in hepatic lipid metabolism induced by two Mn sources in yellow catfish

Understanding the hazards of different forms of metal elements provided innovative insights into their toxicity and environmental risk assessment. To date, few studies had been conducted to investigate the differential effects and mechanisms of MnO2 NPs and MnSO4, two widely distributed environmental pollutants, on hepatic toxicity and lipid metabolism since lipid metabolism-relevant parameters were broadly used as biomarkers for risk assessment of hazardous contaminants. Thus, using yellow catfish Pelteobagrus fulvidraco, an ecologically and economically important freshwater fish as the model, the present study investigated the differential effects and mechanisms of MnO2 NPs and MnSO4 influencing hepatic lipid metabolism. Compared to MnSO4, MnO2 NPs increased hepatic Mn content, induced lipotoxicity, up-regulated the mRNA expression of lipogenic genes, increased peridroplet mitochondrial (PDM) contents, intensified the contact between mitochondria and lipid droplets (LDs), and downregulated miR-20a-5p abundance. Importantly, miR-20a-5p targeted mfn2, which mediated the contact between mitochondria and LDs and influenced changes in lipid metabolism induced by MnO2 NPs. Mechanistically, the direct Mfn2-Plin2 binding and Mfn2 GTPase activity promoted the MnO2 NPs-induced interactions between mitochondria and LDs, which in turn influenced MnO2 NPs-induced changes in hepatic lipid metabolism. For the first time, our findings indicated the significant differences between the changes in body metabolism induced by nanoparticles and inorganic elements, which helped to illuminate different mechanisms governing the responses of aquatic vertebrates to hazardous metal pollutants (MnO2 NPs and MnSO4). MnO2 NPs and MnSO4 are two widely used Mn sources in industries. Their widespread use leads to severe concern about their inevitable discharge into the aquatic environment and thus poses potential threats to aquatic animals. Nevertheless, to date, the different mechanism underlying their toxicities of two Mn sources remains unknown. Here, we elucidated differential mechanisms for the two Mn sources inducing changes in hepatic lipid metabolism via miR-20a-5p targeting mfn2-mediated mitochondria-lipid droplet contacts. Considering that lipid metabolism-relevant parameters are used widely as biomarkers for environmental toxicants, our study is helpful for their toxicological and environmental risk assessment in aquatic ecosystem.