The wonder exerkines—novel insights: a critical state-of-the-art review

Several benefits can be acquired through physical exercise. Different classes of biomolecules are responsible for the cross-talk between distant organs. The secretome of skeletal muscles, and more widely the field of organokines, is ever-expanding. “Exerkine” has emerged as the umbrella term covering any humoral factors secreted into circulation by tissues in response to exercise. This review aims at describing the most interesting exerkines discovered in the last 3 years, which are paving the way for both physiological novel insights and potential medical strategies. The five exerkines identified all play a significant role in the healthy effect of exercise. Specifically: miR-1192, released by muscles and myocardium into circulation, by modulating cardioprotective effect in trained mice; miR-342-5p, located into exosomes from vascular endothelial cells, also a cardioprotective miRNA in trained young humans; apelin, released by muscles into circulation, involved in anti-inflammatory pathways and muscle regenerative capacity in rats; GDF-15, released into circulation from yet unknown source, whose effects can be observed on multiple organs in young men after a single bout of exercise; oxytocin, released by myoblasts and myotubes, with autocrine and paracrine functions in myotubes. The systemic transport by vesicles and the crosstalk between distant organs deserve a deep investigation. Sources, targets, transport mechanisms, biological roles, population samples, frequency, intensity, time and type of exercise should be considered for the characterization of existing and novel exerkines. The “exercise is medicine” framework should include exerkines in favor of novel insights for public health.