Low serum irisin concentration is associated with poor outcomes in patients with acute pancreatitis and irisin administration protects against experimental acute pancreatitis.

Aims: Severe acute pancreatitis (AP) is a serious condition without specific treatment. Mitochondrial dysfunction plays a crucial role in the pathogenesis of AP. Irisin, a novel exercise-induced hormone, contributes to many health benefits of physical activity. We and others have shown that irisin protects against ischemia reperfusion-induced organ injury by alleviating mitochondrial damage. However, the role of irisin in AP has not been evaluated. The purpose of this study was to investigate the role of serum irisin levels in patients with AP and the effect of irisin administration in experimental AP. Results: Serum irisin levels were decreased in AP patients, and low serum irisin levels were associated with worse outcomes in these patients. Treatment with exogenous irisin increased survival and mitigated pancreatic injury in experimental AP. The protective effects of irisin in AP were associated with improvement in mitochondrial function and reduction in ER stress. Moreover, irisin upregulated UCP2 expression in the pancreas, and administration of genipin, a specific UCP2 antagonist, abolished irisin's beneficial effects in L-arginine-induced AP. Innovation and Conclusion: Low serum irisin was associated with poor outcomes in AP patients, and irisin administration protected against experimental AP by restoring mitochondrial function via activation of UCP2. Restoration of mitochondrial function by irisin may offer therapeutic potential for patients with AP.