Perfluorooctanoic acid (PFOA) has applications in numerous industrial products and is an industrial waste that is persistently present in the environment. Exposure to PFOA results in nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanisms remain unclear. In this study, male C57BL/6 mice were exposed to PFOA (1 mg/kg/day) for 4 weeks to evaluate the effect of PFOA, and the human liver cell line (L-02) was used to observe the direct effect of PFOA in vitro. After PFOA exposure, the expression of genes related to hepatic lipogenesis, the NLRP3 inflammasome, and autophagy were measured. We found that exposure to PFOA induced lipid accumulation and stimulated lipogenesis in both mouse livers and L-02 cells. In addition, increased NLRP3 aggregation and enhanced production of IL-1β occurred after PFOA treatment. We also found that PFOA exposure induced autophagosome formation and p62 accumulation, indicating blockage of autophagic flux. Rapamycin alleviated PFOA-induced lipid accumulation and NLRP3 inflammasome activation by activating autophagic flux. Conversely, chloroquine, an autophagic flux inhibitor, exacerbated PFOA-induced lipid accumulation and NLRP3 inflammasome activation. Collectively, these results provide evidence to show that PFOA-induced blockade of autophagic flux causes an increase in lipid synthesis and inflammation in vivo and in vitro.

全氟辛酸 (PFOA) 在许多工业产品中都有应用，是一种长期存在于环境中的工业废物。暴露于 PFOA 会导致非酒精性脂肪肝 (NAFLD)。然而，潜在的机制仍不清楚。在本研究中，雄性 C57BL/6 小鼠暴露于 PFOA（1 mg/kg/天）4 周以评估 PFOA 的作用，并使用人肝细胞系（L-02）观察其直接作用。 PFOA体外. 在 PFOA 暴露后，测量了与肝脂肪生成、NLRP3 炎性体和自噬相关的基因的表达。我们发现暴露于 PFOA 会在小鼠肝脏和 L-02 细胞中诱导脂质积累并刺激脂肪生成。此外，在 PFOA 处理后，NLRP3 聚集增加和 IL-1β 产生增加。我们还发现 PFOA 暴露诱导自噬体形成和 p62 积累，表明自噬通量受阻。雷帕霉素通过激活自噬通量来减轻 PFOA 诱导的脂质积累和 NLRP3 炎性体激活。相反，自噬通量抑制剂氯喹会加剧 PFOA 诱导的脂质积累和 NLRP3 炎性体激活。集体，体内和体外。