Exercise-induced myokines: Molecular mechanisms and systemic health benefits

• Author Details:   
• Harpreet Kour ^*
• Hanjabam Barun Sharma

The skeletal muscle functions as an endocrine organ that secretes bioactive molecules called myokines during exercise. These exercise-induced myokines, including irisin, interleukin-6 (IL-6), and brain-derived neurotrophic factor (BDNF), mediate crosstalk between muscles and distant organs, regulating systemic metabolism, neuroprotection, and inflammation. Irisin, cleaved from FNDC5, induces browning of white adipose tissue and crosses the blood-brain barrier to increase brain-derived neurotrophic factor (BDNF) and synaptic plasticity. Muscle-derived IL-6 exhibits dual roles, stimulating glucose uptake and lipolysis while exerting anti-inflammatory effects by inhibiting TNF-α and inducing IL-1ra and IL-10 production. BDNF, primarily originating from contracting muscle, enhances hippocampal neurogenesis and cognitive function. Myokine secretion exhibits intensity-dependent patterns, with high-intensity interval training (HIIT) preferentially upregulating PGC-1α-dependent myokines, such as irisin. However, knowledge gaps remain regarding myokine receptor systems, temporal dynamics, dose-response relationships, and interindividual variabilities. Methodological challenges include standardization of sampling protocols, utilization of advanced detection methods, and improvement of experimental design and data reporting. Myokines represent a fundamental mechanism underlying the systemic health benefits of exercise and offer therapeutic potential in metabolic and neurodegenerative diseases. Understanding myokine signaling provides critical insights for developing exercise-mimetic therapies and personalized medicine approaches. Future research should on developing myokine biomarkers, optimizing exercise regimens, and exploring pharmacological modulation to harness the endocrine potential of skeletal muscle.