Meteorin-like protein (Metrnl): a key exerkine in exercise-mediated cardiovascular health

Cardiovascular diseases (CVDs) remain a leading global cause of mortality, necessitating non‑pharmacological interventions such as exercise. Meteorin‑like protein (Metrnl), an exercise‑induced myokine and adipokine, has emerged as a critical mediator of exercise‑mediated cardiovascular benefits, though its specific mechanisms and clinical implications remain underexplored. This review synthesizes current evidence on Metrnl's role as a key exerkine in cardiovascular health, focusing on its exercise‑induced regulatory mechanisms, tissue‑specific effects, and therapeutic potential for CVD management. A comprehensive analysis of preclinical and clinical studies was conducted, encompassing molecular, metabolic, and anti‑inflammatory pathways linked to Metrnl. Literature from PubMed, Scopus, and Web of Science was systematically reviewed to evaluate Metrnl's role in exercise‑mediated cardiovascular adaptations. Exercise‑induced Metrnl enhances endothelial function, vascular remodeling, and metabolic regulation via AMPK, PPARγ, and KIT receptor signaling. It promotes glucose/lipid metabolism, angiogenesis, and anti‑inflammatory responses, reducing atherosclerotic risks and improving cardiac repair post‑infarction. Clinically, Metrnl levels correlate with CVD severity, acting as a biomarker for risk stratification. Acute exercise elevates Metrnl, while chronic training effects vary by modality and population. Paradoxically, elevated plasma Metrnl in acute cardiac events predicts adverse outcomes, whereas reduced levels in chronic conditions (e.g., diabetes, heart failure) reflect metabolic dysregulation. Metrnl bridges exercise benefits to cardiovascular health through inter‑organ crosstalk, yet discrepancies exist in its chronic exercise‑mediated regulation. Its dual role as a protective mediator and stress‑responsive biomarker underscores context‑dependent interpretations. Unresolved questions include receptor specificity, tissue autonomy, and therapeutic delivery strategies. Metrnl is a pivotal exerkine with promising diagnostic and therapeutic potential for CVDs. Translating its exercise‑mediated benefits into clinical applications requires further human trials to validate mechanisms and optimize interventions. Harnessing Metrnl could revolutionize strategies for CVD prevention and rehabilitation, leveraging exercise's molecular advantages.