Decreased levels of irisin, a skeletal muscle cell-derived myokine, are related to emphysema associated with chronic obstructive pulmonary disease

BACKGROUND: Cigarette smoking-induced oxidant–antioxidant imbalance is a factor that contributes to the pathogenesis of COPD through epithelial cell apoptosis. Irisin is a skeletal muscle cell-derived myokine associated with physical activity. Irisin is also known to decrease oxidant-induced apoptosis in patients with diabetes mellitus. However, the correlation between irisin and emphysema in COPD and its role in epithelial cell apoptosis remains unknown. SUBJECTS AND METHODS: Forty patients with COPD were enrolled in this study. Pulmonary function tests and measurements of the percentage of low-attenuation area on high-resolution computed tomography images were performed, and the results were evaluated for correlation with serum irisin levels. The effect of irisin on cigarette-smoke extract-induced A549 cell apoptosis and the expression of Nrf2, a transcription factor for antioxidants, was also examined in vitro. RESULTS: Serum irisin levels were significantly correlated with lung diffusing capacity for carbon monoxide divided by alveolar volume (r=0.56, P<0.01) and percentage of low-attenuation area (r=−0.79, P<0.01). Moreover, irisin significantly enhanced Nrf2 expression (P<0.05) and reduced cigarette-smoke extract-induced A549 cell apoptosis (P<0.05). CONCLUSION: Decreased serum irisin levels are related to emphysema in patients with COPD and involved in epithelial apoptosis, resulting in emphysema. Irisin could be a novel treatment for emphysema in patients with COPD.