Bisphenol F (BPF), a substitute for bisphenol A (BPA), is ubiquitous existed in various environmental media. Exposure to BPF may promote non-alcoholic fatty liver disease (NAFLD), while the potential mechanism is still unknown. In current study, we used and model to evaluate its hepatotoxicity and molecular mechanism. Using multi-omics approach, we found that BPF exposure led to changes in hepatic transcriptome, metabolome and chromatin accessible regions that were enriched for binding sites of transcription factors in bZIP family. These alterations were enriched with pathways integral to the endoplasmic reticulum stress and NAFLD. These findings suggested that BPF exposure might reprogram the chromatin accessibility and enhancer landscape in the liver, with downstream effects on genes associated with endoplasmic reticulum stress and lipid metabolism, which relied on bZIP family transcription factors. Overall, our study describes comprehensive molecular alterations in hepatocytes after BPF exposure and provides new insights into the understanding of the hepatoxicity of BPF.

中文翻译：

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多组学方法表征双酚 F 在破坏肝脏脂质代谢中的作用


双酚F（BPF）作为双酚A（BPA）的替代品，普遍存在于各种环境介质中。接触 BPF 可能会促进非酒精性脂肪肝（NAFLD），但潜在机制尚不清楚。在目前的研究中，我们使用 和 模型来评估其肝毒性和分子机制。使用多组学方法，我们发现 BPF 暴露导致肝脏转录组、代谢组和染色质可及区域发生变化，这些区域富含 bZIP 家族转录因子的结合位点。这些改变富含内质网应激和 NAFLD 不可或缺的途径。这些发现表明，BPF 暴露可能会重新编程肝脏中染色质的可及性和增强子景观，并对与内质网应激和脂质代谢相关的基因产生下游影响，这些基因依赖于 bZIP 家族转录因子。总体而言，我们的研究描述了 BPF 暴露后肝细胞的全面分子变化，并为理解 BPF 的肝毒性提供了新的见解。