Polystyrene nanoplastics promote adipogenesis by stimulating nuclear translocation of PPARγ

As an emerging contaminant, nanoplastics (NPs) are widespread in the food chain and environment, raising concerns about their potential toxicity. However, their effects on lipid metabolic homeostasis and the underlying mechanisms remain unclear. This study used polystyrene nanoplastics (PS-NPs), common in food packaging, to examine their impact on adipogenic differentiation and lipid synthesis. Our research results indicated that after 10 days of oral exposure, PS-NPs significantly accumulated in the adipose tissue of mice. Within the exposure concentration range of 1-100 μg/mL, PS-NPs significantly increased the expression of genes related to adipogenesis, accelerated mitotic clonal expansion (MCE) during early differentiation, and enhanced triglyceride (TG) accumulation in mouse 3T3-L1 preadipocytes, leading to adipogenic differentiation and lipogenesis. These effects were positively correlated with the exposure concentration. Protein quantification and immunofluorescence revealed that PS-NPs promoted the nuclear translocation of peroxisome proliferator-activated receptor γ (PPARγ). Molecular dynamics simulations confirmed that PS-NPs bind to the nuclear localization signal (NLS) region of PPARγ. These findings suggested a new molecular mechanism in which PS-NPs influence PPARγ′s subcellular localization through NPs-protein interactions, triggering adipogenic programs. This study provides valuable insights for the safety assessment and toxicology of nanoplastics.