Bisphenol F induces nonalcoholic fatty liver disease-like changes: Involvement of lysosome disorder in lipid droplet deposition
Bisphenol F induces nonalcoholic fatty liver disease-like changes: Involvement of lysosome disorder in lipid droplet deposition
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双酚 F 诱导非酒精性脂肪肝样变化：溶酶体紊乱参与脂滴沉积
DOI：
10.1016/j.envpol.2020.116304
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发表时间：
2021-01-02
影响因子：
8.9
通讯作者：
Gao, Rong
中科院分区：
文献类型：
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作者：
Wang, Jun;Yu, Pengfei;Gao, Rong
流行病学研究表明，一般人群对双酚A（BPA）替代品的暴露是普遍存在的。双酚F（BPF）是BPA的主要替代品之一，在食品和饮料应用中越来越多地取代BPA。越来越多的证据表明，BPA暴露与非酒精性脂肪肝（NAFLD）样变化有关。然而，BPF对脂质稳态的潜在影响仍然知之甚少。在本研究中，流行病学分析与LC-MS-MS显示，血清中的BPF浓度的NAFLD患者显着高于对照组。为了支持这一结果，使用油红O，BODIPY 493/503，LipidTox深红染色和气相色谱-飞行时间质谱（TOF-MS）分析，我们发现BPF暴露诱导小鼠肝脏发生NAFLD样改变，具有明显的脂滴沉积，甘油三酯（TG）和脂肪酸增加。同时，在HepG 2细胞中也观察到BPF诱导的脂滴沉积和TG升高，伴随自噬通量阻断，包括自噬体积累和SQSTM 1/p62降解减少。利用腺病毒双报告质粒RFP-GFP-LC 3、RFP-GFP-PLIN 2转染、AO染色和EGFR降解测定，我们证明BPF处理损害溶酶体降解能力，因为BPF处理明显损害溶酶体酸化，表现为HepG 2和小鼠肝脏组织中溶酶体水解酶组织蛋白酶L（CTSL）和成熟组织蛋白酶D（CTSD）的降低。此外，v-ATP酶D，一种多亚基酶，介导的真核细胞内细胞器的酸化，显着降低后BPF暴露在体外和体内studies.This研究确定了一种新的机制，涉及功能失调的溶酶体降解能力诱导BPF，这有助于脂肪吞噬疾病，并导致脂滴沉积。这项工作提供了证据，溶酶体可能是BPF发挥其潜在毒性的靶细胞器;因此，针对溶酶体的新干预策略有望用于BPF诱导的NAFLD样变化。(C)2020爱思唯尔有限公司保留所有权利。
Epidemiological studies have demonstrated that the general population's exposure to bisphenol A (BPA) substitutes is ubiquitous. Bisphenol F (BPF), one of the main BPA substitutes, is increasingly replacing BPA in plastics for food and beverage applications. Accumulating evidence suggests that BPA exposure is associated with nonalcoholic fatty liver disease (NAFLD)-like changes. However, the potential effects of BPF on lipid homeostasis remain poorly understood. In the present study, an epidemiological analysis with LC-MS-MS revealed that the BPF concentrations in the serum of NAFLD patients were significantly higher than those in a control group. Supporting this result, using Oil Red O, BODIPY 493/503, LipidTox Deep Red staining and gas chromatography-time-of-flight mass spectrometry (TOF-MS) assays, we found that BPF exposure induced NAFLD-like changes, with obvious lipid droplet deposition, triglyceride (TG) and fatty acids increase in mouse livers. Meanwhile, lipid droplet deposition and TG increase induced by BPF were also observed in HepG2 cells, accompanied by autophagic flux blockade, including autophagosome accumulation and the decreased degradation of SQSTMl/p62. Using adenoviruses dual-reporter plasmid RFP-GFP-LC3, RFP-GFP-PLIN2 transfection, AO staining, and EGFR degradation assays, we demonstrated that BPF treatment impaired lysosomal degradative capacity, since BPF treatment obviously impaired lysosomal acidification, manifested as decreased lysosomal hydrolase cathepsin L (CTSL) and mature cathepsin D (CTSD) in HepG2 and mouse liver issues. Additionally, v-ATPase D, a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles, significantly decreased after BPF exposure in both the vitro and in vivo studies.This study ascertained a novel mechanism involving dysfunctional of lysosomal degradative capacity induced by BPF, which contributes to lipophagic disorders and causes lipid droplet deposition. This work provides evidence that lysosomes may be a target organelle where BPF exerts its potential toxicity; therefore, novel intervention strategies targeting lysosome are promising for BPF-induced NAFLD-like changes. (C) 2020 Elsevier Ltd. All rights reserved.