Chronic Waterborne Exposure to Polystyrene Microplastics Induces Kupffer Cell Polarization Imbalance and Hepatic Lipid Accumulation

Microplastics (MPs), particles under 5 mm, are widespread environmental contaminants. Polystyrene (PS), used in many household items, degrades into polystyrene MPs (PS‐MPs), which accumulate in the environment. Chronic exposure to waterborne PS‐MPs was found to disrupt hepatic lipid metabolism in C57BL/6N mice through inflammatory Kupffer cell polarization and IL‐17/NF‐κB signaling pathways. While short‐term PS‐MPs exposure revealed preferential accumulation in the liver and testes, long‐term exposure (9–12 weeks) induced significant increases in body fat percentage and hepatic lipid deposition independent of dietary changes. Mechanistically, chronic PS‐MPs exposure promoted Kupffer cell polarization toward pro‐inflammatory M1 phenotypes, accompanied by upregulated IL‐17 expression and suppressed anti‐inflammatory cytokines. Western blot analysis demonstrated concurrent elevation of lipid synthesis markers with reduced lipid oxidation and transport proteins. These findings established that PS‐MPs accumulation drives hepatic steatosis through dual mechanisms of macrophage‐mediated inflammation and impaired lipid homeostasis pathways.