Microcystins (MCs) produced by cyanobacteria pose serious threats to human health. However, the contribution of long-term exposure to MCs to the development of nonalcoholic fatty liver disease (NAFLD) remains poorly documented. In this study, we estimated the environmental uptake of MCs by a small population of fishers who have lived for many years on Meiliang Bay of Lake Taihu, where cyanobacterial blooms occur frequently. Serum biochemical indices of liver function and their relationships with MC contamination in these people were also investigated. Moreover, to mimic the long-term effects of MC on the livers of fishers, an animal model was established in which mice were exposed to MC-LR at an environmentally relevant level, a reference level (the no-observed adverse effect level, NOAEL), and three times the NOAEL through drinking water for 12 months. We estimated the total daily intake of MCs by fishers through contaminated lake water and food to be 5.95 μg MC-LReq, far exceeding the tolerable daily intake (2.40 μg MC-LReq) proposed by the World Health Organization (WHO). More than 80% of participants had at least one abnormal serum marker. The indices of aspartate aminotransferase (AST)/alanine aminotransferase (ALT), triglyceride (TG), globulin (GLB), and lactate dehydrogenase (LDH) had close positive associations with MC contamination, indicating that both liver damage and lipid metabolism dysfunction were induced by chronic MC exposure. Furthermore, the animal experimental results showed that long-term exposure to MC-LR at the environmentally relevant level led to hepatic steatosis with molecular alterations in circadian rhythm regulation, lipid metabolic processes, and the cell cycle pathway. Exposure to MC-LR at or above the NOAEL worsened the pathological phenotype towards nonalcoholic steatohepatitis disease (NASH) or fibrosis. These results suggest that prolonged exposure to the reference level (NOAEL) of MC-LR could cause severe liver injury to mammals. People with long-term environmental exposure to MCs might be at high risk for developing NAFLD.

蓝细菌产生的微囊藻毒素（MC）对人类健康构成严重威胁。但是，长期暴露于MCs对非酒精性脂肪肝疾病（NAFLD）的发展的贡献仍然很少。在这项研究中，我们估计了在太湖梅梁湾生活了多年的一小部分渔民对MC的环境吸收，那里经常发生蓝细菌开花。还研究了这些人的血清肝功能的生化指标及其与MC污染的关系。此外，为了模拟MC对渔民肝脏的长期影响，建立了一种动物模型，在该模型中，小鼠以与环境相关的水平（参考水平（未观察到的不良反应水平，NOAEL）暴露于MC-LR ），和三倍于NOAEL的饮用水，持续12个月。我们估计渔民通过被污染的湖水和食物每天摄入的MC总量为5.95μgMC-LReq，远远超过了世界卫生组织（WHO）提出的可耐受的每日摄入量（2.40μgMC-LReq）。超过80％的参与者具有至少一种异常的血清标志物。天冬氨酸转氨酶（AST）/丙氨酸转氨酶（ALT），甘油三酸酯（TG），球蛋白（GLB）和乳酸脱氢酶（LDH）的指数与MC污染有密切的正相关性，表明肝损伤和脂质代谢功能障碍均被诱导通过长期的MC暴露。此外，动物实验结果表明，长期暴露于环境相关水平的MC-LR会导致肝脂肪变性，其昼夜节律调节，脂质代谢过程和细胞周期途径的分子改变。在NOAEL或以上暴露于MC-LR会使非酒精性脂肪性肝炎疾病（NASH）或纤维化的病理表型恶化。这些结果表明，长时间暴露于MC-LR的参考水平（NOAEL）可能会对哺乳动物造成严重的肝损伤。长期在环境中接触MC的人群可能罹患NAFLD的风险很高。这些结果表明，长时间暴露于MC-LR的参考水平（NOAEL）可能会对哺乳动物造成严重的肝损伤。长期在环境中接触MC的人可能会患上NAFLD。这些结果表明，长时间暴露于MC-LR的参考水平（NOAEL）可能会对哺乳动物造成严重的肝损伤。长期在环境中接触MC的人群可能罹患NAFLD的风险很高。