MnO₂ nanoparticles and MnSO₄ differentially affected hepatic lipid metabolism through miR-92a/acsl3-dependent de novo lipogenesis in yellow catfish Pelteobagrusfulvidraco

With the increasing production and use of MnO₂ NPs and MnSO₄ in various fields, their discharge into the aquatic environment is inevitable, which poses potential threats to aquatic organisms and humans. However, to date, few studies have been conducted to investigate the potential mechanism of the toxicity of MnO₂ NPs, and a comprehensive understanding of the differences between this mechanism and the toxicity mechanism of inorganic Mn (MnSO₄) is still lacking. Since lipid metabolism-relevant parameters have been widely recognized as novel biomarkers for risk assessment of environmental contaminants, the present study investigated the differential mechanisms of how MnO₂ NPs and MnSO₄ affect hepatic lipid metabolism in a freshwater fish yellow catfish. Compared to MnSO₄, dietary MnO₂ NPs caused liver injury, increased hepatic lipid accumulation and induced lipotoxicity, and up-regulated mRNA expression of de novo lipogenic genes. Moreover, MnO₂ NPs downregulated the expression of miR-92a and miR-92b-3p, microRNAs involved in regulation of lipid metabolism, in the liver. Mechanistically, we found that acls3, an acetyl-coenzyme A synthetase, is target gene of miR-92a, and miR-92a-acsl3-dependent de novo lipogenesis contributes to lipid accumulation and lipotoxicity induced by MnO₂ NPs. Collectively, these findings provided novel insights into mechanism whereby miRNAs mediate nanoparticles- and inorganic Mn-induced hepatic lipotoxicity and changes of lipid metabolism in vertebrates. Our findings also shed new perspective for ecotoxicity and ecological risk of MnO₂ NPs and MnSO₄ in aquatic environment.