Abstract：
Micro- and nanoplastic pollution has emerged as a significant global concern due to their extensive presence in the environment and potential adverse effects on human health. Nanoplastics can enter the human circulatory system and accumulate in the liver, disrupting hepatic metabolism and causing hepatotoxicity. However, the precise mechanism remains uncertain. Lipophagy is an alternative mechanism of lipid metabolism involving autophagy. This study aims to explore how polystyrene nanoplastics (PSNPs) influence lipid metabolism in hepatocytes via lipophagy. Initially, it was found that PSNPs were internalized by human hepatocytes, resulting in decreased cell viability. PSNPs were found to induce the accumulation of lipid droplets (LDs), with autophagy inhibition exacerbating this accumulation. Then, PSNPs were proved to activate lipophagy by recruiting LDs into autophagosomes and block the lipophagic flux by impairing lysosomal function, inhibiting LD degradation. Ultimately, PSNPs were shown to activate lipophagy through the AMPK/ULK1 pathway, and knocking down AMPK exacerbated lipid accumulation in hepatocytes. Overall, these results indicated that PSNPs triggered lipophagy via the AMPK/ULK1 pathway and blocked lipophagic flux, leading to lipid accumulation in hepatocytes. Thus, this study identifies a novel mechanism underlying nanoplastic-induced lipid accumulation, providing a foundation for the toxicity study and risk assessments of nanoplastics.
摘要：
微米和纳米塑料污染已成为全球关注的重要问题，因为它们在环境中的广泛存在以及对人类健康的潜在不利影响。纳米塑料可以进入人体循环系统并积聚在肝脏中，破坏肝脏代谢并引起肝毒性。然而,确切的机制仍然不确定。脂质吞噬是涉及自噬的脂质代谢的替代机制。本研究旨在探讨聚苯乙烯纳米塑料（PSNPs）如何通过脂质吞噬影响肝细胞的脂质代谢。最初，发现PSNP被人肝细胞内化，导致细胞活力下降。PSNP被发现诱导脂滴（LD）的积累，自噬抑制加剧了这种积累。然后，PSNPs被证明通过将LD招募到自噬体内来激活脂质吞噬，并通过损害溶酶体功能来阻断脂质吞噬流，抑制LD降解。最终,PSNP被证明通过AMPK/ULK1途径激活脂质吞噬，敲低AMPK会加剧肝细胞中的脂质积累。总的来说,这些结果表明，PSNPs通过AMPK/ULK1途径触发了吸脂作用并阻断了吸脂通量，导致肝细胞中的脂质积累。因此，这项研究确定了纳米塑料诱导脂质积累的新机制，为纳米塑料的毒性研究和风险评估提供基础。
