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

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.