Bisphenol S Exposure and MASLD: A Mechanistic Study in Mice

作者：Shiqi Li, Yun Fan, Min Tang, Xiaorong Wu, Shengjun Bai, Xiancheng Yang, Xueer Zhang, Chuncheng Lu, Chenbo Ji, Paul A. Wade, Xu Wang, Wei Gu, Guizhen Du, Yufeng Qin · 发表于：Environmental Health Perspectives · 年份：2025 · DOI：10.1289/ehp17057 · 被引用次数：7 · 研究领域：Effects and risks of endocrine disrupting chemicals、Toxic Organic Pollutants Impact、Nutrition, Genetics, and Disease

BACKGROUND: Bisphenol S (BPS) is a substitute for bisphenol A in various commercial products and is increasingly used globally due to restrictions on bisphenol A usage. Consequently, there are increasing public health concerns that substantial effects mediated by synthetic chemicals may impact human health. Recently, epidemiology studies reported associations between bisphenol exposure and nonalcoholic fatty liver disease [metabolic dysfunction-associated steatotic liver disease (MASLD)]. However, the causal relationship and the molecular mechanisms affecting hepatocellular functions are still unknown. OBJECTIVES: Our study aimed to understand the molecular mechanism by which BPS exposure caused hepatic lipid deposition. METHODS: C57BL/6J mice were exposed to BPS for 3 months, and its effects were assessed by histology. RNA sequencing (RNA-seq), assay for transposase-accessible chromatin with high-throughout sequencing (ATAC-seq), and cleavage under targets and tagmentation (CUT&Tag) were used to investigate mechanistic details. ATF3 liver-specific knockout mice and cells were used to validate its functions in BPS-induced hepatotoxicity. RESULTS: significantly attenuates BPS-induced hepatic lipid accumulation via the regulation of chromatin accessibility and gene expression. Besides, inhibiting JunB also eliminates BPS-induced Atf3 upregulation and lipid accumulation. CONCLUSION: Our study reveals a novel mechanism, through which BPS upregulates JunB and Atf3 to impair hepati...