Lv Ziquan, Xu Xinyue, Tang Zhi, Liang Yin, Peng Changfeng, Wu Yuxuan, Sang Dan, Jia Guixuan, Hu Xiaoxiao, Chen Ying, Liu Guangnan, Wang Dan, Huang Suli, Guo Yajie
School of Public Health, University of South China, Hengyang, China.
Division of Conservation and Application of Biological Resources, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
Front Endocrinol (Lausanne). 2025 May 15;16:1571076. doi: 10.3389/fendo.2025.1571076. eCollection 2025.
Bisphenol AF (BPAF), an alternative to Bisphenol A (BPA), is increasingly utilized in various industrial applications, yet its toxicological profile remains incompletely understood. This study aims to investigate the impact of BPAF exposure on obesity and lipid metabolism in male mice subjected to either a normal chow diet (ND) or a high-fat diet (HFD).
Mice were exposed to BPAF at a concentration of 100 μg/kg every other day for five months under different dietary conditions, and body weight, rectal temperature, and food intake were monitored regularly. After the mice were sacrificed, the hepatic lipid metabolism was analyzed by measuring serum, hepatic lipids and performing hepatic metabolomics; energy metabolism was elucidated by assessing thermogenic pathways in brown adipose tissue (BAT) and factors affecting ingestion in the hypothalamus; the development and pathways of obesity were indicated by exploring lipogenesis and lipolysis pathways and fat accumulation in white adipose tissue (WAT).
Histomorphometric analyses indicated that BPAF exposure induced drived fat deposition in white adipose tissue through adipocyte hypertrophy-mediated pathways in eWAT of ND and HFD mice, accompanied by weight gain in HFD mice. Energy metabolism analysis showed that BPAF exposure decreased resting body temperature and reduced thermogenic factor expression in BAT of ND and HFD mice, which may affect energy expenditure. Hepatic metabolomics analysis suggested that BPAF exposure interfered with hepatic lipid metabolism in ND and HFD mice, with elevated levels of hepatic triglycerides, total cholesterol, and free fatty acids in HFD mice. Transcript analysis revealed altered expression levels of genes regulating lipid metabolism in white adipose tissue of ND and HFD mice, with a down-regulation observed in p-HSL protein expression, indicative of a potential inhibition effects of BPAF on lipolysis signaling pathway.
Chronic BPAF exposure differentially exacerbates fat deposition in mice fed normal or high-fat diets via affecting lipid metabolism. Given the widespread prevalence of obesity and the pervasive environmental presence of BPAF, our findings provide valuable insights into the metabolic toxicity of BPAF, thereby raise further concern on the safe utilization and precision prevention of this unique chemical.
双酚AF（BPAF）作为双酚A（BPA）的替代品，在各种工业应用中越来越多地被使用，但其毒理学特征仍未完全了解。本研究旨在调查双酚AF暴露对正常饮食（ND）或高脂饮食（HFD）雄性小鼠肥胖和脂质代谢的影响。
在不同饮食条件下，小鼠每隔一天接受浓度为100μg/kg的双酚AF暴露，持续五个月，并定期监测体重、直肠温度和食物摄入量。小鼠处死后，通过测量血清、肝脏脂质并进行肝脏代谢组学分析肝脏脂质代谢；通过评估棕色脂肪组织（BAT）中的产热途径和下丘脑影响摄食的因素来阐明能量代谢；通过探索白色脂肪组织（WAT）中的脂肪生成和脂肪分解途径以及脂肪积累来表明肥胖的发展和途径。
组织形态计量学分析表明，双酚AF暴露通过ND和HFD小鼠附睾白色脂肪组织（eWAT）中脂肪细胞肥大介导的途径诱导白色脂肪组织中的脂肪沉积，HFD小鼠伴有体重增加。能量代谢分析表明，双酚AF暴露降低了ND和HFD小鼠的静息体温，并降低了BAT中产热因子的表达，这可能会影响能量消耗。肝脏代谢组学分析表明，双酚AF暴露干扰了ND和HFD小鼠的肝脏脂质代谢，HFD小鼠肝脏甘油三酯、总胆固醇和游离脂肪酸水平升高。转录分析显示，ND和HFD小鼠白色脂肪组织中调节脂质代谢的基因表达水平发生改变，p-HSL蛋白表达下调，表明双酚AF对脂肪分解信号通路具有潜在抑制作用。
长期暴露于双酚AF会通过影响脂质代谢，不同程度地加剧正常饮食或高脂饮食喂养小鼠的脂肪沉积。鉴于肥胖的广泛流行以及双酚AF在环境中的普遍存在，我们的研究结果为双酚AF的代谢毒性提供了有价值的见解，从而引发了对这种独特化学物质安全使用和精准预防的进一步关注。
