From Muscle Contraction to Systemic Health: The Emerging Role of Myokines

Introduction and Purpose: Skeletal muscle is increasingly recognized as an endocrine organ that releases signaling molecules involved in systemic regulation. This review summarizes its endocrine function, focusing on myokines, exercise-induced regulation, and relevance to chronic diseases. Material and Method: A narrative literature review was performed using PubMed, Scopus, and Web of Science. Publications from January 2015 to June 2026 were considered, together with earlier landmark studies. The analysis focused on myokine biology, physical activity, inter-organ communication, and clinical applications. Results: Skeletal muscle produces a complex secretome whose composition varies with muscle contraction and metabolic conditions. Selected myokines, including IL-6, irisin, myostatin, IL-15, BDNF, FGF21, and SPARC, have been implicated in metabolic regulation, muscle mass, adipose tissue, inflammation, vascular function, bone metabolism, and nervous system activity. Myokine responses depend on exercise modality, intensity, duration, and individual characteristics. Altered signaling has been reported in chronic diseases. Conclusions: Skeletal muscle endocrine activity contributes to the systemic effects of physical activity. Myokines may mediate metabolic, inflammatory, cardiovascular, musculoskeletal, and neurobiological effects of exercise. However, heterogeneity in study design, analytical methods, and human evidence limits clinical translation. Further well-designed human studies and standardized assessment methods are needed.