There is increasing awareness that exposure to endocrine disrupters interferes with lipid homeostasis in vertebrates, including fish. Many of these compounds exert their action by binding to nuclear receptors, such as peroxisome proliferator-activated receptors and retinoid X receptor. This work investigates the use of fish liver cells (PLHC-1 and ZFL cells) for the screening of metabolic and lipid disrupters in the aquatic environment by assessing changes in the cell’s lipidome after exposure to the model compounds, tributyltin chloride and all-trans retinoic acid. Lipid extracts, analyzed by FIA-ESI (+/-) Orbitrap, evidenced the intracellular accumulation of triglycerides and diglycerides in both cell models after exposure to 100 and 200 nM tributyltin chloride for 24 h. Exposure to 1 μM all-trans retinoic acid led to a significant accumulation of triglycerides in PLHC-1 cells, while few triglycerides were accumulated in ZFL cells. Retinoic acid (cyp26b1, cyp3a65, lrata) and lipid metabolism (fasn, scd, elovl6) related genes were up-regulated by tributyltin chloride and all-trans retinoic acid, while only all-trans retinoic acid down-regulated the expression of dgat1a. The two cell models show sensitivity and responses to tributyltin chloride and all-trans retinoic acid comparable to those previously reported in mammalian cells. These results support the use of fish liver cells as alternative models for the detection of contaminants that act as lipid disrupters in the aquatic environment.

人们越来越认识到，暴露于内分泌干扰物会干扰包括鱼在内的脊椎动物的脂质体内平衡。这些化合物中的许多通过结合核受体（例如过氧化物酶体增殖物激活的受体和类维生素A X受体）发挥作用。这项工作通过评估暴露于模型化合物，氯化三丁锡和全反式维甲酸后细胞脂质组的变化，研究了鱼肝细胞（PLHC-1和ZFL细胞）在水生环境中筛选代谢和脂质破坏物的用途。酸。通过FIA-ESI（+/-）Orbitrap分析的脂质提取物证明，两种细胞模型中的甘油三酸酯和甘油二酸酯在暴露于100和200 nM三丁基氯化锡24小时后在细胞内的积累。暴露于1对μM所有反式维甲酸导致PLHC-1细胞中甘油三酯大量积累，而ZFL细胞中甘油三酯很少积累。维甲酸（cyp26b1，cyp3a65，lrata）和脂质代谢（fasn，scd，ellov16）相关基因被氯化三丁锡和全反式维甲酸上调，而仅全反式维甲酸下调dgat1a的表达。这两种细胞模型显示出对三丁基氯化锡和所有-反式维甲酸与哺乳动物细胞中先前报道的相当。这些结果支持使用鱼肝细胞作为替代模型来检测在水生环境中充当脂质破坏者的污染物。