PFOA暴露通过PPARα信号通路介导的脂质代谢破坏导致肾损伤：一项综合分析。

IF 2.9 3区医学 Q2 TOXICOLOGY

Toxicology letters Pub Date : 2025-09-28 DOI:10.1016/j.toxlet.2025.111736

Yuanyuan Wu , Yuhong Jiang , Zhonghua Fan , Xuan Liu , Weiqiang Sun , Li Wang , Hui Liu

{"title":"PFOA暴露通过PPARα信号通路介导的脂质代谢破坏导致肾损伤：一项综合分析。","authors":"Yuanyuan Wu , Yuhong Jiang , Zhonghua Fan , Xuan Liu , Weiqiang Sun , Li Wang , Hui Liu","doi":"10.1016/j.toxlet.2025.111736","DOIUrl":null,"url":null,"abstract":"<div><div>Perfluorooctanoic acid (PFOA) is a persistent organic pollutant (POP) that can accumulate in living organisms and cause damage to multiple organs and systems in the human body. The kidney is viewed as a key organ affected by PFOA, but the exact mechanism by which PFOA exposure causes kidney damage remains unclear. We selected data from 13,804 participants aged > 12 years old from the National Health and Nutrition Examination Survey (NHANES) database from 2003 to 2018 to analyze the relationship between PFOA and kidney injury. In addition, in the animal experiment, twenty adult male SD rats were divided into four groups randomly: one control group and three PFOA-treated groups. The experiment lasted 28 days, during which time water consumption and urine output were recorded daily. Kidney tissue samples were collected at the end of the experiment. Biochemical assays, RT-qPCR and Western blotting techniques were used to investigate the toxic effects of PFOA exposure on the kidney. Analysis of NHANES data shows a positive correlation between serum PFOA and uric acid (UA) with a β-value of 0.23 (95 % CI: 0.18–0.27) in Model 2. In animal studies, PFOA significantly affected rats’ water intake (increased at 5 mg/kg/d, decreased at 20 mg/kg/d) and urine output (5 > 1.25 > 20 mg/kg/d > control). Renal biochemical analyses revealed significantly lower total cholesterol (TC) (1.25, 20 mg/kg/d groups) and triglyceride (TG) (1.25, 5 mg/kg/d groups) in PFOA-exposed rats. The peroxisome proliferator-activated receptors (PPAR) pathway-related gene/protein levels were significantly altered, such as 900 differentially expressed genes (DEGs) in the 20 mg/kg/d group and upregulated ACOT1 in all PFOA groups. In conclusion, the present study confirms that exposure to PFOA leads to increased oxidative catabolism of fatty acids and impaired renal lipid metabolism. These findings provide an important basis for elucidating the potential health hazards of PFOA.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"413 ","pages":"Article 111736"},"PeriodicalIF":2.9000,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"PFOA exposure causes kidney injury via disruption of lipid metabolism mediated by PPARα signaling pathway: An integrated analysis\",\"authors\":\"Yuanyuan Wu , Yuhong Jiang , Zhonghua Fan , Xuan Liu , Weiqiang Sun , Li Wang , Hui Liu\",\"doi\":\"10.1016/j.toxlet.2025.111736\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Perfluorooctanoic acid (PFOA) is a persistent organic pollutant (POP) that can accumulate in living organisms and cause damage to multiple organs and systems in the human body. The kidney is viewed as a key organ affected by PFOA, but the exact mechanism by which PFOA exposure causes kidney damage remains unclear. We selected data from 13,804 participants aged > 12 years old from the National Health and Nutrition Examination Survey (NHANES) database from 2003 to 2018 to analyze the relationship between PFOA and kidney injury. In addition, in the animal experiment, twenty adult male SD rats were divided into four groups randomly: one control group and three PFOA-treated groups. The experiment lasted 28 days, during which time water consumption and urine output were recorded daily. Kidney tissue samples were collected at the end of the experiment. Biochemical assays, RT-qPCR and Western blotting techniques were used to investigate the toxic effects of PFOA exposure on the kidney. Analysis of NHANES data shows a positive correlation between serum PFOA and uric acid (UA) with a β-value of 0.23 (95 % CI: 0.18–0.27) in Model 2. In animal studies, PFOA significantly affected rats’ water intake (increased at 5 mg/kg/d, decreased at 20 mg/kg/d) and urine output (5 > 1.25 > 20 mg/kg/d > control). Renal biochemical analyses revealed significantly lower total cholesterol (TC) (1.25, 20 mg/kg/d groups) and triglyceride (TG) (1.25, 5 mg/kg/d groups) in PFOA-exposed rats. The peroxisome proliferator-activated receptors (PPAR) pathway-related gene/protein levels were significantly altered, such as 900 differentially expressed genes (DEGs) in the 20 mg/kg/d group and upregulated ACOT1 in all PFOA groups. In conclusion, the present study confirms that exposure to PFOA leads to increased oxidative catabolism of fatty acids and impaired renal lipid metabolism. These findings provide an important basis for elucidating the potential health hazards of PFOA.</div></div>\",\"PeriodicalId\":23206,\"journal\":{\"name\":\"Toxicology letters\",\"volume\":\"413 \",\"pages\":\"Article 111736\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-09-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicology letters\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0378427425026827\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378427425026827","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"TOXICOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

全氟辛酸（PFOA）是一种持久性有机污染物（POP），可在生物体中积累，对人体多个器官和系统造成损害。肾脏被认为是受PFOA影响的关键器官，但PFOA暴露导致肾脏损害的确切机制尚不清楚。我们从2003-2018年国家健康与营养检查调查（NHANES）数据库中选择了13804名年龄在0 - 12岁之间的参与者的数据，分析PFOA与肾损伤之间的关系。另外，在动物实验中，将20只成年雄性SD大鼠随机分为4组：1个对照组和3个pfoa处理组。试验期28 d，每天记录耗水量和排尿量。实验结束时采集肾脏组织样本。采用生化分析、RT-qPCR和Western blotting技术研究PFOA暴露对肾脏的毒性作用。NHANES数据分析显示血清PFOA与尿酸（UA）呈正相关，模型2中β值为0.23 （95% CI: 0.18-0.27）。在动物实验中，PFOA显著影响了大鼠的饮水量（5mg/kg/d时增加，20mg/kg/d时减少）和排尿量（5mg/kg/d、1.25 mg/kg/d、20mg/kg/d、>对照组）。肾脏生化分析显示，pfoa暴露大鼠的总胆固醇（TC）（1.25、20mg/kg/d组）和甘油三酯（TG）（1.25、5mg/kg/d组）显著降低。过氧化物酶体增殖物激活受体（PPAR）通路相关基因/蛋白水平显著改变，如20mg/kg/d组有900个差异表达基因（DEGs），所有PFOA组均上调ACOT1。总之，本研究证实，暴露于PFOA会导致脂肪酸氧化分解代谢增加和肾脏脂质代谢受损。这些发现为阐明PFOA的潜在健康危害提供了重要依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

PFOA exposure causes kidney injury via disruption of lipid metabolism mediated by PPARα signaling pathway: An integrated analysis

Perfluorooctanoic acid (PFOA) is a persistent organic pollutant (POP) that can accumulate in living organisms and cause damage to multiple organs and systems in the human body. The kidney is viewed as a key organ affected by PFOA, but the exact mechanism by which PFOA exposure causes kidney damage remains unclear. We selected data from 13,804 participants aged > 12 years old from the National Health and Nutrition Examination Survey (NHANES) database from 2003 to 2018 to analyze the relationship between PFOA and kidney injury. In addition, in the animal experiment, twenty adult male SD rats were divided into four groups randomly: one control group and three PFOA-treated groups. The experiment lasted 28 days, during which time water consumption and urine output were recorded daily. Kidney tissue samples were collected at the end of the experiment. Biochemical assays, RT-qPCR and Western blotting techniques were used to investigate the toxic effects of PFOA exposure on the kidney. Analysis of NHANES data shows a positive correlation between serum PFOA and uric acid (UA) with a β-value of 0.23 (95 % CI: 0.18–0.27) in Model 2. In animal studies, PFOA significantly affected rats’ water intake (increased at 5 mg/kg/d, decreased at 20 mg/kg/d) and urine output (5 > 1.25 > 20 mg/kg/d > control). Renal biochemical analyses revealed significantly lower total cholesterol (TC) (1.25, 20 mg/kg/d groups) and triglyceride (TG) (1.25, 5 mg/kg/d groups) in PFOA-exposed rats. The peroxisome proliferator-activated receptors (PPAR) pathway-related gene/protein levels were significantly altered, such as 900 differentially expressed genes (DEGs) in the 20 mg/kg/d group and upregulated ACOT1 in all PFOA groups. In conclusion, the present study confirms that exposure to PFOA leads to increased oxidative catabolism of fatty acids and impaired renal lipid metabolism. These findings provide an important basis for elucidating the potential health hazards of PFOA.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊