Abstract
Skeletal muscles secrete various factors, such as proteins/peptides, nucleotides, and metabolites, which are referred to as myokines. Many of these factors are transported into extracellular bodily fluids in a free or protein-bound form. Furthermore, several secretory factors have been shown to be wrapped up by small vesicles, particularly exosomes, secreted into circulation, and subsequently regulate recipient cells. Thus, exosome contents can be recognized as myokines. In recipient cells, proteins, microRNAs, and metabolites in exosomes can regulate the expression and activity of target proteins associated with nutrient metabolism and immune function. The levels of circulating exosomes and their contents are altered in muscle disorders and metabolic-related states, such as metabolic dysfunction, sarcopenia, and physical fitness. Therefore, such circulating factors could mediate various interactions between skeletal muscle and other organs and may be useful as biomarkers reflecting physiological and pathological states associated with muscular function. Here, this review summarizes secretory regulation of muscle-derived exosomes. Their metabolic and immunological roles and the significance of their circulating levels are also discussed.
Highlights
In the last 20 years, skeletal muscle has emerged as a secretory organ
We discussed the roles of exosomes in metabolic and immunological communication between muscles and other organs
Many components are contained in muscle-derived exosomes and are likely contributed to maintaining or impairing the homeostasis of muscles and organs throughout the body
Summary
In the last 20 years, skeletal muscle has emerged as a secretory organ. Early studies showed that interleukin-6 (IL-6) is a typical secretory protein produced by muscle cells [1]. Many secretory factors are transported into the circulation and mediate the communication between skeletal muscle and other organs, referred to as the myokine theory [1]. Myokines can regulate the expression and activity of target proteins in the muscle itself in autocrine and paracrine manners or other organs via an endocrine route, thereby contributing to physiological and pathological phenotypes, such as metabolic capacity, muscle mass, bone density, hormone secretion, cognitive function, and tumorigenesis. Secreted exosomes dock to the plasma membrane of target cells, where they can bind or fuse with the plasma membrane or be endocytosed and deliver their cargo [6]. Skeletal muscle cells secrete exosomes; their contents can be recognized as myokines and have potential functions over freeform secretory factors. We discuss the significance of circulating exosomes and their contents in the context of various physiological, and pathological states, such as muscle disorders, lifestyle-related diseases, and physical fitness
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