Recombinant myonectin ameliorates sepsis‑induced cardiomyopathy by alleviating mitochondrial dysfunction via the AdipoR1/AMPK pathway

Sepsis‑induced cardiomyopathy (SIC) is a common complication of sepsis and is associated with a high mortality rate; however, effective therapies remain lacking. Mitochondrial dysfunction is a key pathogenic mechanism. Myonectin, also known as C1q tumor necrosis factor‑related protein 15, is a novel member of the C1q/TNF‑related protein family. It has been demonstrated to exert cardioprotective effects by suppressing inflammatory response, inhibiting apoptosis and attenuating cardiac fibrosis. Despite these known functions, whether myonectin protects against SIC remains unclear. The present study aimed to investigate the protective potential of recombinant myonectin (rMyonectin) against SIC. Lipopolysaccharide (LPS)‑induced and cecal ligation and puncture‑induced SIC models were established in C57BL/6J mice, and LPS‑stimulated neonatal mouse cardiomyocytes (NMCMs) were used for in vitro validation. Mice and NMCMs were pretreated with rMyonectin prior to the respective challenge. The results showed that rMyonectin improved cardiac function, attenuated myocardial injury, inhibited apoptosis and preserved the integrity of myocardial mitochondria in SIC mice. Furthermore, rMyonectin inhibited LPS‑induced apoptosis in cardiomyocytes. It concurrently promoted mitochondrial biogenesis, maintained mitochondrial dynamics and stabilized mitochondrial membrane potential, thereby improving mitochondrial function and enhancing ATP production. Importantly, these protective effects were abolished by either adiponectin receptor 1 (AdipoR1) knockdown or AMP‑activated protein kinase (AMPK) inhibition. These findings suggest that rMyonectin protects against SIC by alleviating mitochondrial dysfunction via the AdipoR1/AMPK pathway, highlighting its promise as a protective agent.