Key Laboratory of Laboratory Medicine of Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou, 215009, China.
Chemosphere. 2020 Jul;251:126318. doi: 10.1016/j.chemosphere.2020.126318. Epub 2020 Feb 28.
Exposure of endocrine disrupting chemicals (EDCs) is closely related to induction of obesity, nonalcoholic fatty liver disease (NAFLD) and other lipid-metabolism diseases. Herein, we compared the effects of three EDCs exposure (triclosan, bisphenol A and fluorene-9-bisphenol) on lipid metabolism in zebrfish (Danio rerio). The differential lipid-metabolism disorders were analyzed in depth through RNA-Seq and qRT-PCR, as well as assessment of the relationship between lipid disorder and RNA methylation. Histopathological observation along with varying physiological and biochemical indexes all identified that triclosan and bisphenol A induced liver fat accumulation in acute and chronic exposure. RNA-Seq analysis showed that triclosan exposure disrupted multiple physiological processes including drug metabolism, sucrose metabolism, fat metabolism and bile secretion. The dysregulation of lipid-metabolism related genes indicated that liver steatosis in triclosan and BPA-exposed zebrafish resulted from increased fatty acid synthetase, and uptake and suppression of β-oxidation. Besides, the dysregulation of pro-inflammatory genes and endoplasmic reticulum stress showed that triclosan and bisphenol A exposure not only induced occurrence of NAFLD, but also promoted progression of hepatic inflammation. However, no significant effect on lipid metabolism was observed in fluorene-9-bisphenol-exposed treatment although the larval phenotypic malformation was found compared to the control group. Moreover, EDCs exposure led to decreased global mA level and abnormal expression of mA modulators in larvae. Especially, the expression of demethylase FTO (fat mass and obesity-associated protein) was significantly increased in triclosan-exposure treatment. These findings are conductive for us to deeply understand the underlying molecular mechanisms regarding the obesity and NAFLD from EDCs exposure.
内分泌干扰物 (EDCs) 的暴露与肥胖、非酒精性脂肪肝病 (NAFLD) 和其他脂质代谢疾病的发生密切相关。在此，我们比较了三种 EDCs 暴露（三氯生、双酚 A 和芴-9-双酚）对斑马鱼（Danio rerio）脂质代谢的影响。通过 RNA-Seq 和 qRT-PCR 以及脂质紊乱与 RNA 甲基化关系的评估，深入分析了差异脂质代谢紊乱。组织病理学观察以及各种生理和生化指标均表明，三氯生和双酚 A 在急性和慢性暴露下诱导肝脏脂肪堆积。RNA-Seq 分析表明，三氯生暴露破坏了包括药物代谢、蔗糖代谢、脂肪代谢和胆汁分泌在内的多个生理过程。脂质代谢相关基因的失调表明，三氯生和 BPA 暴露的斑马鱼肝脏脂肪变性是由于脂肪酸合成酶的增加以及β氧化的摄取和抑制所致。此外，促炎基因和内质网应激的失调表明，三氯生和双酚 A 的暴露不仅诱导了 NAFLD 的发生，而且促进了肝炎症的进展。然而，与对照组相比，尽管在氟芴-9-双酚暴露处理中发现了幼鱼表型畸形，但在氟芴-9-双酚暴露处理中并未观察到对脂质代谢有显著影响。此外，EDCs 暴露导致幼鱼全局 mA 水平降低和 mA 调节剂表达异常。特别是，三氯生暴露处理中去甲基酶 FTO（肥胖相关蛋白）的表达显著增加。这些发现有助于我们深入了解 EDCs 暴露导致肥胖和 NAFLD 的潜在分子机制。
