Acute PM2.5 Exposure Exacerbates Mitochondrial Dysfunction and Structural Damage in Skeletal Muscle of Type 2 Diabetic Mice

PURPOSE: This study aimed to investigate whether PM2.5 exposure further increases mitochondrial dysfunction and structural damage in skeletal muscle under type 2 diabetes.METHODS: Type 2 diabetic mice (DM) were generated by feeding a high-fat diet to a polygenic diabetic mouse model (NSY x C57BL/6). Mice were divided into four groups: Wild-type mice exposed to filtered air (WT-CON), WT mice exposed to PM2.5 (WTPM2.5), DM exposed to filtered air (DM-CON), and DM exposed to PM2.5 (DM-PM2.5). PM2.5 (52.7±8.9 μg/m3) was administered for 2 h/day for 5 days a week, followed by a 4-week recovery period. Skeletal muscle samples were analyzed for glucose metabolism, mitochondrial biogenesis protein expression, and mitochondrial morphology by ttechnical error of measurement (TEM).RESULTS: PM2.5 exposure significantly increased GLUT-4 expression in DM, whereas glycolytic enzymes (HXK-2, PFK-1, and LDH) remained unchanged. PGC-1α–Tfam signaling was partially activated, accompanied by elevated COX-1 expression, suggesting compensatory mitochondrial biogenesis. However, concurrent upregulation of PINK1, Parkin, Bax, and Bcl-2 revealed sustained mitochondrial stress and incomplete recovery. TEM analysis confirmed severe mitochondrial morphological damage, including cristae disruption and matrix swelling, in the DM+PM2.5 group.CONCLUSIONS: PM2.5 exposure further exacerbates the imbalance in energy metabolism and mitochondrial damage in skeletal muscle under type 2 diabetes conditions.