Lipidomics and transcriptomics insight into impacts of microplastics exposure on hepatic lipid metabolism in mice

Microplastics (MPs), the emerging environmental pollutants, have attracted global attention due to the potential public health challenge and ecological security risk. Recent studies suggested liver as a vulnerable organ to MPs exposure, evidenced by abnormal hepatic lipid metabolism upon MPs intake in multiple animal species. However, the specific changes of lipid metabolism in mammalian livers, as well as the underlying mechanisms, remain to be elucidated. In the present study, C57BL/6 mice were randomly assigned to normal drinking water or drinking water containing 100 μg L^-1 or 1000 μg L^-1 polystyrene (PS) MPs for 8 weeks. MPs exposure exerted no significant effect on body weight, serum triglyceride or total cholesteryl esters. However, mice showed impaired glucose tolerance and hepatic lipid deposition in response to high-dose MPs administration. Further lipidomic analysis showed significant alteration in hepatic lipid species particularly with free fatty acids (FFAs) and triacylglycerols (TAGs) in mice exposed to MPs. Meanwhile, the liver transcriptional profile indicated MPs exposure-induced differentially expressed genes (DEGs) were enriched in pathways of lipid metabolism and unfolded protein response. Furthermore, most altered lipid species were significantly correlated with DEGs enriched in lipid metabolic signaling. These findings provide lipidomic and transcriptional signatures of liver in response to MPs exposure, which will shed light on further understanding of the metabolic toxicity of MPs.