Large polystyrene microplastics results in hepatic lipotoxicity in mice

Like small microplastics (MPs), recent studies reveal that large MPs could cause health risks in mice, even if they are not enriched in tissues. However, potential hepatoxicity following large MPs exposure and the underlying mechanisms have not been thoroughly investigated. In the present study, we explored the disruption of hepatic lipid metabolism and potential underlying toxic mechanisms in mice caused by long-term exposure to large polystyrene MPs (40–100 μm) based on a multi-omic approach. After 21 weeks of feeding foods containing MPs (50 and 500 mg/kg food), lipidomic revealed that environmentally relevant and higher doses MP exposures resulted in significant changes in a total of 20 lipid classes. Ceramide (Cer) and dihydroceramide (dhCer) were significantly reduced, while cholesteryl ester (CE), lysoalkylphosphatidylcholine (LPCO), lysophosphatidylethanolamine (LPE) and total glyceride (TG) were all elevated by MPs. The transcriptomic and other physiological data suggested that the potential toxic mechanisms may be related to disorders of fatty acid and cholesterol synthesis and metabolism disorders, and transporting of TG. Our findings demonstrate the hepatic lipotoxicity following exposure to environmentally relevant and higher doses of large MPs, calling for future research and management of the environmental risks of MPs with relatively large particle sizes. [Display omitted] •Large MPs resulted in hepatic lipotoxicity in mice.•Large MPs induced oxidative stress in the liver.•Large MPs decreased hepatic phospholipids and sphingolipids.•Large MPs increased glycerolipids and sterols.•Large MPs caused lipid changes associated with NAFLD.