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氯菊酯暴露通过氧化应激介导的 KRAS-PPAR-GLUT 信号通路影响斑马鱼的脂质代谢。

Permethrin exposure impacts zebrafish lipid metabolism via the KRAS-PPAR-GLUT signaling pathway, which is mediated by oxidative stress.

机构信息

School of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu Province, China 212013.

School of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu Province, China 212013.

出版信息

Aquat Toxicol. 2024 Aug;273:107021. doi: 10.1016/j.aquatox.2024.107021. Epub 2024 Jul 8.

Abstract

Permethrin (Per) is a widely used and frequently detected pyrethroid pesticide in agricultural products and the environment. It may pose potential toxicity to non-target organisms. Per has been reported to affect lipid homeostasis, although the mechanism is undefined. This study aims to explore the characteristic transcriptomic profiles and clarify the underlying signaling pathways of Per-induced lipid metabolism disorder in zebrafish liver. The results showed that environmental exposure to Per caused changes in the liver index, histopathology, and oxidative stress in zebrafish. Moreover, transcriptome results showed that Per heavily altered the pathways involved in metabolism, the immune system, and the endocrine system. We conducted a more in-depth analysis of the genes associated with lipid metabolism. Our findings revealed that exposure to Per led to a disruption in lipid metabolism by activating the KRAS-PPAR-GLUT signaling pathways through oxidative stress. The disruption of lipid homeostasis caused by exposure to Per may also contribute to obesity, hepatitis, and other diseases. The results may provide new insights for the risk of Permethrin to aquatic organisms and new horizons for the pathogenesis of hepatotoxicity.

摘要

氯菊酯(Permethrin,Per)是一种广泛应用且在农产品和环境中经常被检测到的拟除虫菊酯类农药。它可能对非靶标生物产生潜在的毒性。已有报道称,氯菊酯会影响脂质稳态,但其机制尚未明确。本研究旨在探索氯菊酯诱导的斑马鱼肝脂质代谢紊乱的特征转录组图谱,并阐明其潜在的信号通路。结果表明,环境暴露于氯菊酯会导致斑马鱼肝指数、组织病理学和氧化应激发生变化。此外,转录组结果表明,氯菊酯大量改变了代谢、免疫系统和内分泌系统相关的途径。我们对与脂质代谢相关的基因进行了更深入的分析。我们的研究结果表明,氯菊酯通过氧化应激激活 KRAS-PPAR-GLUT 信号通路,导致脂质代谢紊乱。氯菊酯暴露引起的脂质稳态破坏也可能导致肥胖、肝炎等疾病。这些结果可能为氯菊酯对水生生物的风险提供新的见解,并为肝毒性的发病机制开辟新的视野。

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