Persistent Exposure to Environmental Levels of Microcystin-LR Disturbs Cortisol Production via Hypothalamic-Pituitary-Interrenal (HPI) Axis and Subsequently Liver Glucose Metabolism in Adult Male Zebrafish (Danio rerio)
Persistent Exposure to Environmental Levels of Microcystin-LR Disturbs Cortisol Production via Hypothalamic-Pituitary-Interrenal (HPI) Axis and Subsequently Liver Glucose Metabolism in Adult Male Zebrafish (Danio rerio)
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持续暴露于环境水平的微囊藻毒素-LR 会干扰成年雄性斑马鱼（斑马鱼）通过下丘脑-垂体-肾间 (HPI) 轴产生的皮质醇以及随后的肝脏葡萄糖代谢
DOI：
10.3390/toxins12050282
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发表时间：
2020-04
期刊：
影响因子：
4.2
通讯作者：
Tang Rong
中科院分区：
文献类型：
--
作者：
Wang Lingkai;Lin Wang;Zha Qingji;Guo Honghui;Zhang D;an;Yang Liping;Li Li;Li Dapeng;Tang Rong
越来越多的证据表明，微囊藻毒素-LR(MC-LR)是一种新的内分泌干扰物，但持续暴露MC-LR对下丘脑-垂体-肾间轴(HPI)的影响及其对健康的危害尚未被研究。将成年雄性斑马鱼(Danio Rerio)分别浸泡在浓度为0、1、5和25μg/L的MC-LR溶液中30d。结果表明，持续的MC-LR暴露引起HPI轴基因的广泛上调，但抑制了脑核受体(GR和MR)，最终导致血清皮质醇水平上升。此外，肝脏糖皮质激素受体的表达降低可能与糖异生相关基因(PEPCK、fbp1a、g6pca)、糖原分解相关基因(PYG)、糖酵解相关基因(gk、pfk1b、pk)和糖异生相关基因(Gys2)的表达受到强烈抑制有关。这些发现与血糖的下降是一致的，表明长期接触MC-LR导致葡萄糖产量低于葡萄糖裂解。我们的上述结果首次建立了持续的MC-LR暴露与糖代谢受损之间的联系，表明长期MC-LR介导的应激可能威胁鱼类的健康。
There is growing evidence that microcystin-LR (MC-LR) is a new endocrine disruptor, whereas the impacts of persistent exposure to MC-LR on the hypothalamic-pituitary-interrenal (HPI) axis and health hazards thereafter have not been investigated. In this work, adult male zebrafish (Danio rerio) were immersed into MC-LR solutions at concentrations of 0, 1, 5 and 25 μg/L for 30 d, respectively. The results showed that persistent MC-LR exposure caused an extensive upregulation of HPI-axis genes but an inhibition of brain nuclear receptors (gr and mr), which finally increased serum cortisol levels. Furthermore, the decreased expression of hepatic gr might partly be responsible for the strong inhibition on the expression of downstream genes involved in glucose metabolic enzymes, including gluconeogenesis-related genes (pepck, fbp1a, g6pca), glycogenolysis-related gene (pyg), glycolysis-related genes (gk, pfk1b, pk) and glycogenesis-related gene (gys2). These findings are in accordance with the decline in serum glucose, indicating that long-term MC-LR exposure caused a lower production of glucose relative to glucose lysis. Our above results firstly establish the link between persistent MC-LR exposure and impaired glucose metabolism, suggesting that long-term MC-LR-mediated stress might threaten fish’s health.
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