Inter‐Organ Crosstalk and Regulatory Mechanisms of Skeletal Muscle‐Derived Extracellular Vesicles in Systemic Metabolic Homeostasis

Extracellular vesicles (EVs), including exosomes, play a pivotal role in intercellular communication by facilitating the transfer of bioactive molecules between cells. These vesicles, which encompass a variety of subtypes such as exosomes, microvesicles and apoptotic bodies, carry functional proteins, mRNAs, miRNAs and other molecular cargo that influence various physiological processes. In particular, skeletal muscle-derived EVs have recently emerged as a novel category of myokines, contributing to muscle homeostasis through paracrine signalling and exerting systemic endocrine effects on metabolic tissues, including the pancreas, adipose tissue and liver. This review systematically examines the regulatory mechanisms of skeletal muscle-derived EVs, with particular focus on exosomes, in mediating inter-organ crosstalk. Additionally, it examines the factors that influence the release of skeletal muscle-derived EVs, particularly exosomes and their subsequent effects on metabolism.