Distinctive lipidomic responses induced by polystyrene micro- and nano-plastics in zebrafish liver cells.

Despite growing awareness of the size-dependent toxicity caused by micro- and nano-plastics (MNPs) in fish, the modulation of the liver lipidome as a function of particle size has not been thoroughly investigated. This study explores the subcellular and molecular responses induced by polystyrene microplastics (MPs, 1 µm) and nano-plastics (NPs, 52 nm) in zebrafish liver (ZFL) cells, with a focus on the modulation of the cell's lipidome and gene expression profiles. Both particle sizes are readily internalized by ZFL cells; however, NPs had a more pronounced impact compared to MPs. Lipidomic analysis revealed that MPs decreased polyunsaturated phospholipids, while NPs increased ether-linked phosphatidylcholines (PC-Ps/PCOs). Gene expression analysis showed that high concentrations of MPs down-regulated the expression of fatty acid synthesis related genes, and significantly downregulated the microsomal triglyceride transfer protein (mtp) gene, indicating a perturbation in lipid storage metabolism, which was not observed for NP exposure. In contrast, NPs induced a dose-dependent accumulation of lipids, suggesting increased lipid droplet formation and an activation of ceramide-mediated apoptosis pathway. These findings provide new insights into the molecular mechanisms of MNP toxicity and emphasize the importance of considering particle size when assessing environmental and health risks. Furthermore, this study highlights the potential of lipidomics for elucidating the mechanisms underlying MNP toxicity, prompting further research into of the long-term consequences of exposure.