Abstract Background Acute respiratory distress syndrome (ARDS) is one of the leading causes of intensive care unit (ICU) admission and is associated with substantial mortality. In addition to acute lung injury (ALI) induced respiratory failure during the acute phase, muscle wasting is frequently observed in patients with ARDS and contributes to ICU-acquired weakness, which is strongly linked to poor outcomes and delayed recovery. Irisin, a myokine released from skeletal muscle during exercise, plays an essential role in regulating energy metabolism and attenuating inflammatory responses, and is believed to preserve muscle mass by enhancing myogenesis and inhibiting muscle atrophy. This study aims to explore the therapeutic potential of irisin in ARDS, focusing on its dual capacity to improve both respiratory and muscle health. Methods We integrated clinical, cellular, and animal evidence to evaluate irisin as a translational intervention for ARDS-associated ALI and muscle loss. First, circulating irisin levels and muscle parameters were analyzed in a clinical cohort of ICU patients with ARDS. Next, an in vitro C2C12 myoblast model was employed to validate the protective effects of irisin against Lipopolysaccharide (LPS)-induced impairment of myotube formation. Finally, mice subjected to intratracheal (i.t.) LPS-induced ALI received intravenous administration of irisin recombinant protein, followed by histological, molecular, and functional assessments of both lung and skeletal muscle including the quadriceps, gastrocnemius, and tibialis anterior. Results In the clinical cohort, circulating irisin levels were significantly lower in patients with ARDS than in healthy controls. In C2C12 myoblasts, irisin treatment accelerated myotube formation under LPS-exposure conditions. In mice subjected to i.t. LPS, irisin simultaneously reduced the severity of ALI and mitigated muscle atrophy, as evidenced by preserved muscle fiber morphology characterized by rounder fibers on histological examination. Conclusion Irisin concurrently alleviated pulmonary injury and muscle wasting in endotoxin-induced ALI, underscoring its translational potential to enhance both respiratory recovery and long-term muscle health in patients with ARDS. This abstract is funded by: None
Shen et al. (Fri,) studied this question.