Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, 86011, USA.
Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, 86011, USA.
Environ Pollut. 2019 Aug;251:390-399. doi: 10.1016/j.envpol.2019.05.001. Epub 2019 May 2.
Perchlorate is a pervasive, water-soluble contaminant that competitively inhibits the sodium/iodide symporter, reducing the available iodide for thyroid hormone synthesis. Insufficient iodide uptake can lead to hypothyroidism and metabolic syndromes. Because metabolism, obesity and non-alcoholic fatty liver disease (NAFLD) are tightly linked, we hypothesized that perchlorate would act as an obesogen and cause NAFLD via accumulation of lipids in liver of developing threespine stickleback (Gasterosteus aculeatus). We performed an upshift/downshift exposure regime (clean water to perchlorate treated water or perchlorate treated water to clean water) on stickleback embryos at two concentrations (30 mg/L and 100 mg/L) plus the control (0 mg/L) over the course of 305 days. Adult stickleback were euthanized, H&E stained and analyzed for liver morphology. Specifically, we counted the number of lipid droplets, and measured the area of each droplet and the total lipid area of a representative section of liver. We found that perchlorate treated fish had more and larger lipid droplets, and a larger percentage of lipid in their liver than control fish. These data indicate that perchlorate causes NAFLD and hepatic steatosis in stickleback at concentrations commonly found at contaminated sites. These data also indicate the potential of perchlorate to act as an obesogen. Future studies should investigate the obesogenic capacity of perchlorate by examining organ specific lipid accumulation and whether perchlorate induces these effects at concentrations commonly found in drinking water. Work is also needed to determine the mechanisms by which perchlorate induces lipid accumulation.
高氯酸盐是一种普遍存在的、水溶性的污染物，它竞争性地抑制钠/碘转运体，减少甲状腺激素合成所需的碘。碘摄入不足可导致甲状腺功能减退和代谢综合征。由于代谢、肥胖和非酒精性脂肪肝（NAFLD）紧密相关，我们假设高氯酸盐可能作为一种肥胖物，通过在发育中的三刺鱼（Gasterosteus aculeatus）肝脏中积累脂质而导致 NAFLD。我们对三刺鱼胚胎进行了上调/下调暴露处理（从清洁水到高氯酸盐处理水或从高氯酸盐处理水到清洁水），在 305 天的过程中，使用了两个浓度（30mg/L 和 100mg/L）和对照（0mg/L）进行处理。成年三刺鱼被安乐死，进行 H&E 染色，并对肝脏形态进行分析。具体来说，我们计算了脂质滴的数量，并测量了每个脂质滴的面积和肝脏代表性切片的总脂质面积。我们发现，高氯酸盐处理的鱼的肝脏中脂质滴更多、更大，并且脂质含量比对照鱼高。这些数据表明，高氯酸盐在常见的污染地点浓度下，可导致三刺鱼发生 NAFLD 和肝脂肪变性。这些数据还表明高氯酸盐有作为肥胖物的潜力。未来的研究应通过检查特定器官的脂质积累，以及高氯酸盐是否在饮用水中常见浓度下诱导这些效应，来研究高氯酸盐的肥胖能力。还需要开展工作以确定高氯酸盐诱导脂质积累的机制。
