Nano- and microplastics induce size specific adipogenic and metabolic dysregulation

The widespread presence of nano- and microplastics (NMPs) in the environment and their detection in human tissues raise concerns about their potential metabolic impacts. While previous studies have focused on NMPs toxicity, the size-dependent effects of NMPs on adipogenesis remain poorly understood. Adipocyte differentiation in 3T3-L1 cells was investigated using environmentally relevant NMPs sizes (200 nm, 2 μm and 20 μm), representing 10-fold size increments under non-cytotoxic conditions (50 μg/mL). Smaller NMPs (200 nm and 2 μm) were associated with uptake-related pathways linked to caveolin-mediated endocytosis and macropinocytosis, respectively, and were accompanied by increased lipid accumulation, glucose uptake, adiponectin expression, and adipogenic marker activation. Internalized NMPs induced mitochondrial overload, characterized by elevated ROS, altered respiratory activity, proton leak, membrane depolarization, and impaired mitochondrial dynamics. Molecular docking revealed that styrene monomers and dimers, bind PPARγ and CD36, supporting their role as functional mimetics in adipogenic signaling. In contrast, larger particles (20 μm), which remain extracellular, trigger only modest lipid accumulation and mild pro-inflammatory responses via NFκB1 signaling. Our findings highlight particle size as a determinant of NMP-induced metabolic disruption in adipocytes, linking internalization to metabolic dysfunction and identifying PPARγ signaling and mitochondrial pathways as possible therapeutic targets for NMP-induced adipose dysfunction.