Yang Ming, An Ziwen, Xing Xiaoqing, Mei Yayuan, Li Haoran, Zhao Jiaxin, Tan Zhenzhen, Li Yanbing, Zhao Jingjing, Zhao Jiayin, Zhao Meiduo, Xu Jing, Xu Qun, Guo Huicai, Li Ang
Center for Rare Diseases, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China; Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
Department of Toxicology, School of Public Health, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Environment and Human Health, Shijiazhuang, Hebei 050017, China.
J Hazard Mater. 2025 Sep 15;496:139257. doi: 10.1016/j.jhazmat.2025.139257. Epub 2025 Jul 16.
Diabetes and kidney diseases are complex disorders influenced by organ-specific abnormalities and systemic dysregulation. Previous research suggests per- and polyfluoroalkyl substances (PFAS) can interfere with glucose metabolism and kidney function, but their impact on pancreas-kidney inter-organ crosstalk is unclear. In this study, we conducted a three-wave repeated-measures analysis, in a non-diabetic, non-chronic kidney disease (CKD) cohort. We assessed 23 PFAS, 23 amino acids, 5 glucose indicators, and 3 renal biomarkers across three visits. Our findings showed that perfluorooctane sulfonate (PFOS) was linked to both glucose and renal biomarkers, suggesting its potential role in impairing pancreas-kidney crosstalk. We also identified amino acids, particularly serine and citrulline, as key mediators in this process, implicating amino acid metabolism as a common mechanism through which PFOS influences inter-organ communication. Serine was found to positively mediate approximately 50 % of the total effect of PFOS exposure on insulin and glucose metabolism, while citrulline negatively mediated about 15 % of PFOS's effects on kidney function biomarkers. These results highlight PFOS's role in disrupting pancreas-kidney crosstalk within a non-diabetic, non-CKD cohort and provide new insights into amino acid regulation in metabolic and kidney diseases. This is the first study to demonstrate PFAS involvement in this inter-organ crosstalk and suggests a novel mechanism involving amino acids.
糖尿病和肾脏疾病是受器官特异性异常和全身失调影响的复杂疾病。先前的研究表明，全氟和多氟烷基物质（PFAS）会干扰葡萄糖代谢和肾功能，但其对胰腺-肾脏器官间串扰的影响尚不清楚。在本研究中，我们在一个非糖尿病、非慢性肾病（CKD）队列中进行了三波重复测量分析。我们在三次访视中评估了23种PFAS、23种氨基酸、5种血糖指标和3种肾脏生物标志物。我们的研究结果表明，全氟辛烷磺酸（PFOS）与血糖和肾脏生物标志物均有关联，表明其在损害胰腺-肾脏串扰方面的潜在作用。我们还确定氨基酸，特别是丝氨酸和瓜氨酸，是这一过程中的关键介质，这意味着氨基酸代谢是PFOS影响器官间通讯的共同机制。研究发现，丝氨酸正向介导了PFOS暴露对胰岛素和葡萄糖代谢总效应的约50%，而瓜氨酸负向介导了PFOS对肾功能生物标志物约15%的影响。这些结果突出了PFOS在非糖尿病、非CKD队列中破坏胰腺-肾脏串扰的作用，并为代谢性疾病和肾脏疾病中的氨基酸调节提供了新的见解。这是第一项证明PFAS参与这种器官间串扰的研究，并提出了一种涉及氨基酸的新机制。
