Chronic, Environmentally Relevant PM2.5 Exposure Exacerbates Metabolic Dysfunction-Associated Steatotic Liver Disease and Early-Stage Renal Dysfunction in a Rodent Model.

While epidemiological studies link fine particulate matter (PM2.5) exposure to metabolic dysfunction-associated steatotic liver disease (MASLD) and renal dysfunction, a translational gap exists, as most animal models utilize acute, high-dose exposures that poorly reflect chronic, moderate-level human scenarios. To address this, we established a long-term (seven-month) mouse model (n = 8 per group) combining a Western diet (WD) with a chronic PM2.5 exposure paradigm equivalent to a human exposure of ~50 μg/m3, assessing key biomarkers, organ histopathology, and hepatic gene expression. While the WD was the primary driver of MASLD-related steatosis and insulin resistance, PM2.5 co-exposure acted as a distinct modifier of hepatic pathogenesis. Specifically, the WD + PM group exhibited significantly exacerbated hepatic pathology compared to WD alone, characterized by a ~55% increase in serum ALT (p < 0.05) and a 4.7-fold increase in collagen deposition area (p < 0.05), alongside the marked upregulation of pro-inflammatory (TNF-α, CCL2) and pro-fibrotic (α-SMA, COL1A1) genes. In the kidney, PM2.5 exposure independently elevated serum creatinine levels (by ~64% vs. controls, p < 0.05) and increased the incidence of proteinuria (75% in WD + PM vs. 0% in controls). These functional alterations occurred without inducing major structural damage. This study provides crucial experimental evidence that moderate, chronic air pollution aggravates diet-induced hepatic inflammation/fibrosis and contributes to early-stage renal dysfunction, underscoring the multi-organ health threats to metabolically vulnerable populations.