Targeting AMPK with Irisin: Implications for metabolic disorders, cardiovascular health, and inflammatory conditions - A systematic review.

Irisin-based interventions have gained attention for their potential to modulate the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway in various diseases. Physiologically, irisin is a myokine released during physical exercise that exerts anti-inflammatory effects and is a metabolic and cardiometabolic enhancer. On the other hand, AMPK is crucial for maintaining energy balance and metabolic homeostasis. Therefore, individuals presenting low blood levels of irisin and AMPK dysregulation are more predisposed to metabolic disorders and cardiovascular health inflammatory conditions since regulating energy balance and metabolic homeostasis are crucial for preventing or treating these disorders. In light of those mentioned above and considering that no review has addressed the intricate relationships between irisin and AMPK regulation in the realm of metabolic disorders, cardiovascular health, and inflammatory conditions, we comprehensively reviewed studies involving irisin's effects on AMPK signaling in different models and interventions. Our systematic analysis involved in vitro studies, animal models, and their relevant clinical implications of irisin targeting AMPK due to the absence of relevant clinical trials. The outcomes and limitations of the included studies were extensively highlighted. Objectively, irisin improved metabolic disorders by enhancing β-cell function and insulin secretion in diabetes, mitigating myocardial injury in cardiovascular conditions, and reducing inflammation and oxidative stress in various injury models by targeting AMPK. However, the lack of clinical trials limits the generalizability of these findings to human subjects. Future research should focus on translating these findings into clinical applications and exploring the broader implications of irisin-based interventions in human health.