The search for exercise factors in humans

Abstract

Regular exercise reduces the risk for numerous chronic diseases. Exercise not only impacts the contracting skeletal muscle but also elicits systemic changes. The exact mechanisms driving the more systemic changes have yet to be resolved, but exercise factors are thought to be an important missing link. Exercise factors are proteins that are released from skeletal muscle into the circulation during exercise. They represent a subclass of myokines, which are classified as proteins secreted from skeletal muscle serving a signaling role. Here, we provide an overview of the current literature on myokines. Many studies have focused on the identification of new myokines using a variety of approaches. These studies have generated an extensive list of myokines, but so far, the functional relevance of many of these novel myokines remains unclear. Few of these myokines represent putative exercise factors. Currently, IL-6, secreted protein acidic and rich in cysteine, angiopoietin-like 4, chemokine (C-X3-C motif) ligand 1, and chemokine (C-C motif) ligand 2 have the highest potential to serve as exercise factors because for all these factors, there is clear evidence that plasma levels increase during exercise. In our view, the future focus should be on characterizing the functional role of myokines in the acute and chronic response to exercise and explore their potential as a target for metabolic diseases.

Musclin is an activity-stimulated myokine that enhances physical endurance

“…Such coordination has been attributed in part to the action of myokines. Specifically, "exercise factors," a subset of myokines whose production and secretion into systemic circulation are stimulated by physical activity, have been shown to modulate skeletal muscle and systemic metabolism, angiogenesis, growth, and inflammation (14).…”

Multiplex Quantification Identifies Novel Exercise-regulated Myokines/Cytokines in Plasma and in Glycolytic and Oxidative Skeletal Muscle

“…The underlying mechanisms responsible for the positive physiological effects of exercise, however, are not well understood (7,8). The systemic effects of exercise on multi-organ systems has long thought to be, at least in part, due to myokines and cytokines secreted by skeletal muscle in response to exercise (9)(10)(11). These exercise-induced myokines are believed to mediate crosstalk between skeletal muscle and other organ compartments.…”

Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise

“…However, insulin does not promote glucose catabolism and its circulating levels decline during exercise (Coderre et al, 1995;Lund et al, 1995). This suggests that the rise in nutrients uptake and in their catabolism in muscle that occurs during exercise may be favored by other secreted molecules, myokines (Catoire and Kersten, 2015) or hormones, the circulating levels of which would increase during exercise. Conceivably, myokines and hormones may cooperate to favor adaptation to exercise.…”