Qi Weipeng, Clark John M, Timme-Laragy Alicia R, Park Yeonhwa
Department of Food Science, University of Massachusetts, Amherst, MA, 01003, United States.
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, 01003, United States.
Toxicol Environ Chem. 2020;102(10):585-606. doi: 10.1080/02772248.2020.1808894. Epub 2020 Aug 26.
Per- and poly-fluoroalkyl substances, especially perfluorooctanesulfonic acid, 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, the major replacement for perfluorooctanesulfonic acid, on non-alcoholic fatty liver disease. Therefore, the effects of perfluorobutanesulfonic acid exposure on fat accumulation in a human hepatoma cell line were examined. Cells were exposed to perfluorobutanesulfonic acid 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 hours. Perfluorobutanesulfonic acid 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. Perfluorobutanesulfonic acid upregulated key genes controlling lipogenesis and fatty acid uptake. Perfluorobutanesulfonic acid treatment also promoted the production of reactive oxygen species, an endoplasmic reticulum stress marker and cytosolic calcium. In conclusion, perfluorobutanesulfonic acid increased fat accumulation, in part, via peroxisome proliferator-activated receptor gamma-mediated pathway in hepatoma cells.
全氟和多氟烷基物质，尤其是全氟辛烷磺酸，已经被广泛使用了50多年。越来越多的证据表明这些物质具有潜在的不良影响，包括其对非酒精性脂肪性肝病（最常见的慢性肝病之一）发展的影响。尽管如此，关于全氟辛烷磺酸的主要替代品全氟丁烷磺酸对非酒精性脂肪性肝病影响的报道尚未出现。因此，研究了全氟丁烷磺酸暴露对人肝癌细胞系脂肪积累的影响。将细胞暴露于含有或不含有300μmol/L脂肪酸混合物（油酸：棕榈酸=2:1）与牛血清白蛋白结合作为脂肪变性诱导剂的全氟丁烷磺酸中48小时。与对照组相比，200μmol/L的全氟丁烷磺酸在有脂肪酸存在时显著增加了甘油三酯水平，但在无脂肪酸时则没有，这种增加被一种特异性过氧化物酶体增殖物激活受体γ拮抗剂所消除。全氟丁烷磺酸上调了控制脂肪生成和脂肪酸摄取的关键基因。全氟丁烷磺酸处理还促进了活性氧、内质网应激标志物和胞质钙的产生。总之，全氟丁烷磺酸部分通过过氧化物酶体增殖物激活受体γ介导的途径增加了肝癌细胞中的脂肪积累。
