Abstract
<jats:p>Skeletal muscle is increasingly recognised as a key component of the musculoskeletal system, in addition to being a vital, metabolically active endocrine organ that plays a central role in regulating whole-body energy homeostasis. Skeletal muscle communicates with various visceral tissues through the secretion of contraction-induced myokines, metabolites, and neurohormonal signals that establish complex bidirectional crosstalk with organs such as the liver, adipose tissue, pancreas, gut, and brain. This intricate network facilitates metabolic flexibility, enabling the body to adapt efficiently to different physiological and environmental demands. In health, this muscle–organ communication orchestrates processes essential for maintaining energy balance, glucose regulation, lipid metabolism, and overall metabolic health. However, in pathological conditions – including obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), cancer cachexia, chronic kidney disease (CKD), and critical illness – the normal regulatory mechanisms become disrupted, leading to maladaptive signalling. These perturbations contribute to systemic dysfunction and disease progression. This chapter synthesises the current understanding of muscle–organ crosstalk and highlights how these interactions are altered in disease. Clinical implications are emphasised, particularly in peri-operative and critical care contexts, including prehabilitation, nutrition strategies, and emerging therapies targeting the exercise–myokine axis.</jats:p>