Qiao Wenying, Li Jiashuo, Luo Lijia, Peng Wenjuan, Wang Xi, Jin Ronghua, Li Junnan
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing institute of infectious disease, Beijing 100015, China.
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
Ecotoxicol Environ Saf. 2025 Jan 1;289:117436. doi: 10.1016/j.ecoenv.2024.117436. Epub 2024 Dec 4.
Nonalcoholic fatty liver disease (NAFLD) is recognized as a significant public health problem worldwide. Several clinical studies have investigated the associations between Per- and poly-fluoroalkyl substances (PFAS) compounds with the risk of NAFLD in general adults, but the mediating effect of triglycerides (TG) was remained unexplored. In this study, 6990 individuals from the National Health and Nutrition Examination Survey (NHANES, 2003-2018) database were enrolled. Firstly, the results of generalized linear models (GLM) and restricted cubic splines (RCS) revealed positive associations of PFAS compounds with NAFLD risk score and liver function, and nearly linear E-R curves indicated no safe threshold. Meanwhile, weighted quantile sum (WQS) regression demonstrated the relationships between PFAS mixtures with NAFLD risk score and liver function, as well as perfluorooctanoic acid (PFOA) was identified as the main contributor to the increased NAFLD risk. Then, mediation analysis was conducted to explore whether serum lipids mediate the relationships. It further highlighted significant mediation effects of TG, with the mediated proportion ranging from 10.4 % to 42.9 %. Finally, sensitivity and stratified analyses were performed, confirming the reliability of these findings. Notably, significant associations were observed in individuals with a BMI ≥ 28, highlighting that these relationships were particularly evident in obese participants. In conclusion, our study suggested that PFAS mixtures exposure may influence NAFLD risk score by mediating TG in human metabolism. This result could provide more comprehensive epidemiological evidence and guide clinical applications.
非酒精性脂肪性肝病（NAFLD）被公认为全球重大的公共卫生问题。多项临床研究调查了全氟和多氟烷基物质（PFAS）化合物与一般成年人患NAFLD风险之间的关联，但甘油三酯（TG）的中介作用仍未得到探索。在本研究中，纳入了来自美国国家健康与营养检查调查（NHANES，2003 - 2018）数据库的6990名个体。首先，广义线性模型（GLM）和受限立方样条（RCS）的结果显示PFAS化合物与NAFLD风险评分和肝功能呈正相关，且近乎线性的暴露 - 反应（E - R）曲线表明不存在安全阈值。同时，加权分位数和（WQS）回归证明了PFAS混合物与NAFLD风险评分和肝功能之间的关系，并且全氟辛酸（PFOA）被确定为NAFLD风险增加的主要贡献因素。然后，进行中介分析以探讨血脂是否介导这些关系。结果进一步突出了TG的显著中介作用，中介比例在10.4%至42.9%之间。最后，进行了敏感性和分层分析，证实了这些发现的可靠性。值得注意的是，在体重指数（BMI）≥28的个体中观察到显著关联，这突出表明这些关系在肥胖参与者中尤为明显。总之，我们的研究表明，PFAS混合物暴露可能通过介导人体代谢中的TG来影响NAFLD风险评分。这一结果可为临床应用提供更全面的流行病学证据并提供指导。
