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.