Cross-Organ Toxicity and Metabolic Responses to Food Chain-Transferred Nanoplastics: Mechanistic Insights from a...

Against the backdrop of escalating global plastic pollution, there is an urgent need to elucidate the systemic health risks posed by nanoplastics (NPs) as emerging environmental contaminants that enter higher organisms through the food chain. This study employed a three-level trophic transfer model, examining the pathway from polystyrene nanoparticles to Tenebrio molitor larvae and subsequently to mice, offering a comprehensive elucidation of the mechanisms behind the multiorgan toxicity associated with food chain-transferred nanoplastics (FCT-NPs). Our results demonstrated extensive accumulation of FCT-NPs across multiple organs via systemic circulation. Integrative multiorgan omics analysis revealed that FCT-NPs primarily induced two major categories of multiorgan comorbidities: cardiovascular diseases and metabolic disorders, with the liver identified as a central metabolic hub that potentially regulates other organs through bile acid-mediated metabolic crosstalk. Mechanistically, dysregulation of key genes, such as MTOR and FN1, activated Wnt and TGF-β signaling pathways, which in turn promoted organ fibrosis. Additionally, aberrant expression of critical regulators─including CAT, LPL, NQO1, and APOE─was found to drive oxidative stress and disrupt lipid metabolism. These findings provide crucial scientific evidence for FCT-NPs risk assessment and underscore the imperative for enhanced plastic pollution control and further investigation into long-term exposure effects.