Hubei Hongshan Laboratory, Fishery College, Huazhong Agricultural University, Wuhan, 430070, China.
Hubei Hongshan Laboratory, Fishery College, Huazhong Agricultural University, Wuhan, 430070, China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China.
Environ Pollut. 2023 Nov 1;336:122416. doi: 10.1016/j.envpol.2023.122416. Epub 2023 Aug 18.
With the increasing production and use of MnO NPs and MnSO 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 MnO NPs, and a comprehensive understanding of the differences between this mechanism and the toxicity mechanism of inorganic Mn (MnSO) 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 MnO NPs and MnSO affect hepatic lipid metabolism in a freshwater fish yellow catfish. Compared to MnSO, dietary MnO NPs caused liver injury, increased hepatic lipid accumulation and induced lipotoxicity, and up-regulated mRNA expression of de novo lipogenic genes. Moreover, MnO 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 MnO 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 MnO NPs and MnSO in aquatic environment.
随着 MnO NPs 和 MnSO 在各个领域的产量和使用增加，它们不可避免地排放到水环境中，对水生生物和人类构成潜在威胁。然而，迄今为止，很少有研究探讨 MnO NPs 毒性的潜在机制，对其与无机 Mn（MnSO）毒性机制的差异也缺乏全面了解。由于脂质代谢相关参数已被广泛认为是环境污染物风险评估的新型生物标志物，本研究探讨了 MnO NPs 和 MnSO 如何影响淡水鱼黄颡鱼肝脏脂质代谢的差异机制。与 MnSO 相比，膳食 MnO NPs 导致肝脏损伤、肝内脂质积累增加和诱导脂毒性，并上调了新生脂质生成基因的 mRNA 表达。此外，MnO NPs 下调了肝脏中参与脂质代谢调节的 microRNA miR-92a 和 miR-92b-3p 的表达。从机制上讲，我们发现 acsl3，一种乙酰辅酶 A 合成酶，是 miR-92a 的靶基因，miR-92a-acsl3 依赖性新生脂质生成有助于 MnO NPs 诱导的脂质积累和脂毒性。总之，这些发现为 miRNA 介导的纳米颗粒和无机 Mn 诱导的肝脂毒性以及脊椎动物脂质代谢变化的机制提供了新的见解。我们的研究结果也为 MnO NPs 和 MnSO 在水生环境中的生态毒性和生态风险提供了新的视角。
