Polystyrene nanoplastics inhibit beige fat function and exacerbate metabolic disorder in high-fat diet-fed mice

Global health concerns about micro- and nanoplastics are increasing. The newly discovered beige adipocytes play a vital role in energy homeostasis through their high thermogenic capacity upon activation. However, the effects of micro- and nanoplastics on beige adipocytes have not yet been studied. We investigated whether the effects of oral exposure to polystyrene nanoparticles (PS-NPs) on systemic metabolic performance can be induced by disrupting beige adipocyte function, and the potential mechanism. In the present study, C57BL/6J male mice were fed a high-fat diet (HFD) with or without PS-NPs exposure for 12 weeks to investigate the differences in metabolic performance. We also isolated stromal vascular fraction from C57BL/6J male mice to differentiate and prepare primary beige adipocyte cultures. Primary beige adipocytes were treated with PS-NPs on the sixth day of differentiation. The results showed that oral intake of PS-NPs exacerbated metabolic disorders of mice under HFD, including suppressed energy expenditure, increased fat mass and liver steatosis, decreased insulin sensitivity, disrupted glucose homeostasis, and decreased cold-tolerance capability compared with the control group. Intriguingly, we observed that, after a 12-week exposure, PS-NPs accumulated in the inguinal white adipose tissue (iWAT), a fat depot rich in beige adipocytes, further suppressing thermogenic gene programs, particularly the level of uncoupling protein 1 (UCP1), a master regulator in the browning process of beige adipocytes. These effects ultimately led to decreased energy expenditure and subsequent disorders of glucolipid metabolism. Mechanistically, we revealed that PS-NPs disrupt mitochondrial function and induce oxidative damage and inflammation in beige adipocytes to inhibit their function. These negative metabolic effects of PS-NPs were ameliorated by antioxidant supplementation. Our study is the first to demonstrate that PS-NPs exposure exacerbates metabolic disorder in HFD-fed mice by disrupting beige adipocyte function.