Multi-omics approach characterizes the role of Bisphenol F in disrupting hepatic lipid metabolism

• Published in: Environment international 2024-05, Vol.187, p.108690, Article 108690
• Main Authors: Fan, Yun, Li, Shiqi, Yang, Xiancheng, Bai, Shengjun, Tang, Min, Zhang, Xueer, Lu, Chuncheng, Ji, Chenbo, Du, Guizhen, Qin, Yufeng
• Format: Article
• Language: English
• Subjects: Animals; Benzhydryl Compounds - toxicity; Bisphenol F; Chromatin accessibility; Endoplasmic reticulum stress; Endoplasmic Reticulum Stress - drug effects; Hepatocytes - drug effects; Hepatocytes - metabolism; Humans; Lipid Metabolism - drug effects; Liver - drug effects; Liver - metabolism; Male; Mice; Multi-omics; Multiomics; NAFLD; Non-alcoholic Fatty Liver Disease - chemically induced; Non-alcoholic Fatty Liver Disease - metabolism; Phenols - toxicity; Transcriptome - drug effects
• ISSN: 0160-4120; 1873-6750; 1873-6750
• DOI: 10.1016/j.envint.2024.108690

[Display omitted] •Multi-omics approach uncovers the hepatotoxicity and mechanism of BPF.•BPF exposure remodels hepatic chromatin structure and transcriptome.•BPF exposure alters genes involved in ER stress and lipid metabolism pathway. 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 in vitro and in vivo 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.