Muscle as a paracrine and endocrine organ

•Skeletal muscle secretes myokines that exert autocrine paracrine and endocrine effects.•Paracrine factors modulate muscle angiogenesis, adipogenesis, and innervation.•Myokine secretion is regulated by exercise.•Exercise benefits cardiovascular, metabolic and mental health via endocrine factors.•The molecular mechanisms regulating myokine secretion remain to be fully elucidated.

Skeletal muscle cells are highly abundant and metabolically active and are known to 'communicate' their energy demands to other organs through active secretion. Muscle-derived secretory proteins include a variety of cytokines and peptides collectively referred to as 'myokines' that exert autocrine, paracrine or endocrine effects. Analyses of the skeletal muscle secretome revealed that numerous myokines are secreted in response to contraction or strength training, and that these factors not only regulate energy demand but also contribute to the broad beneficial effects of exercise on cardiovascular, metabolic, and mental health. Herein we review recent studies on the myokines that regulate muscle function and those that mediate cross talk between skeletal muscle and other organs including adipose tissue, liver, pancreas, the cardiovascular system, brain, bones, and skin.