Microplastics (MP) derived from the weathering of polymers, or synthesized in this size range, have become widespread environmental contaminants and have found their way into water supplies and the food chain. Despite this awareness, little is known about the health consequences of MP ingestion. We have previously shown that the consumption of polystyrene (PS) beads was associated with intestinal dysbiosis, diabetes, and obesity in mice. To further evaluate the systemic metabolic effects of PS on the gut-liver-adipose tissue axis, we supplied C57BL/6J mice with normal water or that containing two sizes of PS beads (0.5mm and 5mm) at a concentration of 1mg/ml. After 13wk, we evaluated several indices of metabolism and liver function. As previously observed, mice drinking the PS-containing water had a potentiated weight gain and adipose expansion. Here we found that this was associated with an increased abundance of adipose F4/80⁺ macrophages. These exposures did not cause non-alcoholic fatty liver disease (NAFLD) but were associated with decreased liver:body weight ratios and an enrichment in hepatic FXR and LXR signaling. PS also increased hepatic cholesterol and altered both hepatic and cecal bile acids. Mice consuming PS beads and treated with the berry anthrocyanin, delphinidin, demonstrated an attenuated weight gain compared to those mice receiving a control intervention and also exhibited a down-regulation of cAMP and PPAR signaling pathways. This study highlights the obesogenic role of PS in perturbing the gut-liver-adipose axis and altering nuclear receptor signaling and intermediary metabolism. Dietary interventions may limit the adverse metabolic effects of PS consumption.  

To perform the adipose transcriptomic analysis, RNA was prepared from tissue sections using a miRNeasy kit (Qiagen). Concentrations were determined using a NanoDrop instrument (Thermo Scientific). RNAseq and data analysis utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG, Gene Ontology classifications (GO), and the Reactome Database was performed by Novogene.