Journal
ENVIRONMENTAL POLLUTION
Volume 336, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.envpol.2023.122416
Keywords
Nanoparticles; Biomarkers; miRNAs; Lipid metabolism; Lipotoxicity; Vertebrates
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This study investigated the differential mechanisms of how MnO2 NPs and MnSO4 affect hepatic lipid metabolism in a freshwater fish. MnO2 NPs caused liver injury, increased hepatic lipid accumulation, and induced lipotoxicity, while up-regulating the expression of de novo lipogenic genes. In addition, MnO2 NPs downregulated the expression of microRNAs involved in the regulation of lipid metabolism. Mechanistically, miR-92a-acsl3-dependent de novo lipogenesis contributed to lipid accumulation and lipotoxicity induced by MnO2 NPs.
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 miR92a, 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.
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