Exercise-Induced Myokines With Therapeutic Potential for Muscle Wasting

Abstract

Skeletal muscle is a highly vascularized tissue that can secrete proteins called myokines. These muscle-secreted factors exert biological functions in muscle itself (autocrine effect) or on short- or long-distant organs (paracrine/endocrine effects) and control processes such as metabolism, angiogenesis, or inflammation. Widely differing diseases ranging from genetic myopathies to cancers are emerging as causing dysregulated secretion of myokines from skeletal muscles. Myokines are also involved in the control of muscle size and may be important to be restored to normal levels to alleviate muscle wasting in various conditions, such as cancer, untreated diabetes, chronic obstructive pulmonary disease, aging, or heart failure. Interestingly, many myokines are induced by exercise (muscle-derived exerkines) and some even by specific types of physical activity, but more studies are needed on this issue. Most exercise-induced myokines travel throughout the body by means of extracellular vesicles. Restoring myokines by physical activity may be added to the list of mechanisms by which exercise exerts preventative or curative effects against a large number of diseases, including the deleterious muscle wasting they may cause. Extending our understanding about which myokines could be usefully restored in certain diseases might help in prescribing more tailored exercise or myokine-based drugs.

Exercise and metabolic health: beyond skeletal muscle

“…For example, levels of brain-derived neurotrophic factor (BDNF), proteins belonging to the natriuretic peptide family (e.g. B-type natriuretic peptide [BNP]), musclin, IL-15, IL-6, apelin, secreted protein acidic and rich in cysteine (SPARC), fibroblast growth factor 21 (FGF-21), decorin, myonectin and irisin have been shown to increase in the circulation in response to exercise and these molecules are likely to play a role in the control of muscle mass and skeletal muscle metabolism in an autocrine fashion, as reviewed elsewhere [36,37]. The effect of some of these molecular factors have been studied in rodents or in in vitro Fig.…”

Physical Activity-Dependent Regulation of Parathyroid Hormone and Calcium-Phosphorous Metabolism

“…Members of the family are IL-6, IL-11, leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), oncostatin M (OSM), and ciliary neurotrophic factor (CNTF). Each cytokine that binds to gp130 generates specific intracellular JAK/STAT or ERK signaling cascades by forming specific receptor: ligand complexes [ 227 , 228 ]. Osteocyte-targeted deletion of gp130 was found to ablate the anabolic response to PTH in trabecular bone and on the periosteum [ 229 ].…”

Impact of Melatonin on Skeletal Muscle and Exercise

“…Emerging evidence indicates that a progressive resistance program better than acute oxidative exercise is crucial to preserve mobility in aged patients, thus retarding the onset of frailty and related metabolic and cardiovascular diseases [143]. Another beneficial role of exercise is the secretion of muscular cytokines, called myokines, which regulate multiple biological functions [144].…”