Polystyrene Microplastics and Lead Co-Exposure Disturbed Hepatic Lipid Metabolism in C57BL/6 Mice

<b>Background:</b> Microplastics and lead are ubiquitous pollutants in the environment, frequently found in soil, water and food. Although the toxicity of individual exposure to microplastics and lead has been well studied, research on their co-exposure effects is still emerging. <b>Methods:</b> In this study, we investigated the impacts of polystyrene microplastics and lead co-exposure on hepatic lipid metabolism through transcriptomics and untargeted lipidomics profiling in C57BL/6 mice. <b>Results:</b> Gene set enrichment analysis of the transcriptomics data revealed the fatty acid metabolism was significantly disrupted by the co-exposure in male mice. Consistently, pathway analysis of lipidomics data showed that several fatty acid pathways were activated by the co-exposure in male mice, including fatty acid (20:1) → fatty acid (22:1) → fatty acid (24:1), fatty acid (20:0) → fatty acid (22:0) → fatty acid (24:0), fatty acid (18:1) → fatty acid (18:2) → fatty acid (20:2), fatty acid (18:1) → fatty acid (18:2) → fatty acid (18:3) → fatty acid (18:4); meanwhile, fatty acid (18:4) → fatty acid (20:4) → fatty acid (22:4), fatty acid (18:4) → fatty acid (20:4) → fatty acid (20:5) were suppressed. Transition from diacylglycerol to phosphatidylethanolamine and from phosphatidylserine to phosphatidylethanolamine were activated by the co-exposure in male mice; meanwhile transition from phosphatidylserine to phosphatidylethanolamine was activated in female mice. <b>Conclusions</b>: Our findings suggested that hepatic lipid metabolism was disturbed by the co-exposure of polystyrene microplastics and lead, which provide insights into the combined exposure risks of microplastics and heavy metals.