Abstract Per- and poly-fluoroalkyl substances, especially perfluorooctanesulfonic acid (PFOS), have been extensively used for over 50 years. A growing body of evidence has emerged demonstrating the potential adverse effects of these substances, including its effect on the development of non-alcoholic fatty liver disease, as one of the most prevalent chronic liver diseases. Nonetheless, there is no report of effects of perfluorobutanesulfonic acid (PFBS), the major replacement for PFOS, on non-alcoholic fatty liver disease. Therefore, the effects of PFBS exposure on fat accumulation in a human hepatoma cell line were examined. Cells were exposed to PFBS with or without 300 μmol/L fatty acid mixture (oleic acid–palmitic acid, 2:1) conjugated by bovine serum albumin as an inducer of steatosis for 48 h. PFBS at 200 μmol/L significantly increased the triglyceride level in the presence of fatty acid compared to the control, but not without fatty acid, which was abolished by a specific peroxisome proliferator-activated receptor gamma antagonist. PFBS upregulated key genes controlling lipogenesis and fatty acid uptake. PFBS treatment also promoted the production of reactive oxygen species, an endoplasmic reticulum stress marker and cytosolic calcium. In conclusion, PFBS increased fat accumulation, in part, via peroxisome proliferator-activated receptor gamma-mediated pathway in hepatoma cells. Abbreviations: ACC: acetyl-CoA carboxylase; CD36: cluster of differentiation 36; CHOP: CCAAT/enhancer-binding homologous protein; CPT1α: carnitine palmitoyltransferase 1α; DDIT3: DNA damage-inducible transcript 3; DGAT2: diacylglycerol O-acyltransferase 2; ER: endoplasmic reticulum; FA: fatty acid; FAS: fatty acid synthase; NAFLD: nonalcoholic fatty liver disease; NF-κB: nuclear factor kappa B; PFAS: per- and polyfluoroalkyl substances; PFBS: perfluorobutanesulfonic acid; PFOS: perfluorooctanesulfonic acid; PPAR: peroxisome proliferator-activated receptor; ROS: reactive oxygen species; SREBP1: sterol regulatory element-binding protein 1; TG: triglyceride; TNF-α: tumor necrosis factor alpha; UPR: unfolded protein response

中文翻译：

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全氟丁烷磺酸 (PFBS) 在 HepG2 人肝癌中诱导脂肪堆积

摘要 全氟和多氟烷基物质，尤其是全氟辛烷磺酸 (PFOS)，已被广泛使用 50 多年。越来越多的证据表明这些物质的潜在不利影响，包括其对非酒精性脂肪性肝病发展的影响，非酒精性脂肪性肝病是最普遍的慢性肝病之一。尽管如此，没有关于全氟丁烷磺酸 (PFBS)（全氟辛烷磺酸的主要替代品）对非酒精性脂肪性肝病的影响的报告。因此，研究了 PFBS 暴露对人肝癌细胞系中脂肪积累的影响。将细胞暴露于含有或不含 300 μmol/L 脂肪酸混合物（油酸-棕榈酸，2:1）的 PFBS 中，该混合物由牛血清白蛋白作为脂肪变性的诱导剂共轭 48 小时。与对照相比，200 μmol/L 的 PFBS 在存在脂肪酸的情况下显着增加了甘油三酯水平，但在没有脂肪酸的情况下则不然，这种情况被特定的过氧化物酶体增殖物激活受体 γ 拮抗剂所消除。PFBS 上调控制脂肪生成和脂肪酸摄取的关键基因。PFBS 处理还促进了活性氧的产生，这是一种内质网应激标记物和细胞溶质钙。总之，PFBS 增加了脂肪积累，部分原因是肝细胞瘤细胞中过氧化物酶体增殖物激活受体 γ 介导的途径。缩写：ACC：乙酰辅酶A羧化酶；CD36：分化簇36；CHOP：CCAAT/增强子结合同源蛋白；CPT1α：肉碱棕榈酰转移酶1α；DDIT3：DNA 损伤诱导转录物 3；DGAT2：二酰基甘油O-酰基转移酶2；急诊室：内质网；FA：脂肪酸；FAS：脂肪酸合酶；NAFLD：非酒精性脂肪肝；NF-κB：核因子κB；PFAS：全氟和多氟烷基物质；PFBS：全氟丁烷磺酸；PFOS：全氟辛烷磺酸；PPAR：过氧化物酶体增殖物激活受体；ROS：活性氧；SREBP1：甾醇调节元件结合蛋白1；TG：甘油三酯；TNF-α：肿瘤坏死因子α；UPR：未折叠蛋白反应 甘油三酯；TNF-α：肿瘤坏死因子α；UPR：未折叠蛋白反应 甘油三酯；TNF-α：肿瘤坏死因子α；UPR：未折叠蛋白反应