Arginine Metabolism Reprogramming in Perfluorooctanoic Acid (PFOA)-Induced Liver Injury

IF 10.8 1区环境科学与生态学 Q1 ENGINEERING, ENVIRONMENTAL

环境科学与技术 Pub Date : 2025-01-10 DOI:10.1021/acs.est.4c07971

Jie Gao, Tiantian Li, Wei Guo, Meilin Yan, Junran Liu, Xiaolong Yao, Meilin Lv, Yun Ding, Hua Qin, Minghao Wang, Runzeng Liu, Jun Liu, Chunzhen Shi, Jianbo Shi, Guangbo Qu, Guibin Jiang

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Abstract

Perfluorooctanoic acid (PFOA) is a persistent pollutant that has gained worldwide attention, owing to its widespread presence in the environment. Previous studies have reported that PFOA upregulates lipid metabolism and is associated with liver injury in humans. However, when the fatty acid degradation pathway is activated, lipid accumulation still occurs, suggesting the presence of unknown pathways and mechanisms that remain to be elucidated. In this study, adult C57BL/6N mice were exposed to PFOA at 0.1, 1, and 10 mg/kg/day. Using integrated metabolomics and transcriptomics, it was uncovered that arginine metabolism was differentially downregulated in all three groups. In vitro studies confirmed the downregulation of arginine metabolism in MIHA cell lines treated with PFOA. Supplementation of arginine could effectively rescue liver injury and downregulate the chemokine levels caused by PFOA. This finding highlights the contribution of arginine metabolism in maintaining liver health following PFOA exposure and suggests potential mechanisms of metabolic and immune modulation.

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全氟辛酸（PFOA）诱导的肝损伤中精氨酸代谢重编程

全氟辛酸（PFOA）是一种持久性污染物，由于其在环境中的广泛存在而引起了全世界的关注。先前的研究报道了PFOA上调脂质代谢并与人类肝损伤有关。然而，当脂肪酸降解途径被激活时，脂质积累仍然发生，这表明存在未知的途径和机制有待阐明。在本研究中，成年C57BL/6N小鼠以0.1、1和10 mg/kg/天的剂量暴露于PFOA。利用综合代谢组学和转录组学，发现在所有三组中精氨酸代谢都存在差异下调。体外研究证实，经PFOA处理的MIHA细胞系精氨酸代谢下调。补充精氨酸可以有效地挽救PFOA引起的肝损伤，并下调趋化因子水平。这一发现强调了精氨酸代谢在PFOA暴露后维持肝脏健康中的作用，并提出了代谢和免疫调节的潜在机制。

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来源期刊

环境科学与技术环境科学-工程：环境

CiteScore

17.50

自引率

9.60%

发文量

12359

审稿时长

2.8 months

期刊介绍： Environmental Science & Technology (ES&T) is a co-sponsored academic and technical magazine by the Hubei Provincial Environmental Protection Bureau and the Hubei Provincial Academy of Environmental Sciences. Environmental Science & Technology (ES&T) holds the status of Chinese core journals, scientific papers source journals of China, Chinese Science Citation Database source journals, and Chinese Academic Journal Comprehensive Evaluation Database source journals. This publication focuses on the academic field of environmental protection, featuring articles related to environmental protection and technical advancements.