Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Shanxi Provincial Center for Disease Control and Prevention, Taiyuan 030012, Shanxi, China.
J Hazard Mater. 2024 Sep 5;476:134878. doi: 10.1016/j.jhazmat.2024.134878. Epub 2024 Jun 10.
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.
微塑料和纳米塑料污染因其在环境中的广泛存在及其对人类健康的潜在不良影响而成为一个重大的全球性问题。纳米塑料可以进入人体循环系统并在肝脏中积累，扰乱肝脏代谢并导致肝毒性。然而，其确切的机制尚不清楚。脂噬作用是一种涉及自噬的脂质代谢的替代机制。本研究旨在通过脂噬作用探讨聚苯乙烯纳米塑料（PSNPs）如何影响肝细胞中的脂质代谢。最初发现 PSNPs 被人肝细胞内吞，导致细胞活力下降。PSNPs 被发现诱导脂滴（LDs）的积累，自噬抑制会加剧这种积累。然后，PSNPs 通过将 LDs 招募到自噬体中并通过损害溶酶体功能来阻断脂噬流来证明激活脂噬作用，从而抑制 LD 降解。最终，PSNPs 通过 AMPK/ULK1 途径激活脂噬作用，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 途径触发脂噬作用并阻断脂噬流，导致肝细胞中的脂质积累。因此，本研究确定了纳米塑料诱导脂质积累的一种新机制，为纳米塑料的毒性研究和风险评估提供了基础。
