Myokines: Motion Is Lotion?

Ryan Argetsinger, 7/14/24

Physical activity and exercise are known to be recommended forms of disease prevention by the CDC, but the particulars for this recommendation are now being fully discovered and researched. Previously known as “exercise factors,” myokines are produced from skeletal muscle activation and released into circulation in the form of interleukin-6 (IL-6). IL-6 has been shown to have several metabolic and immunologic effects throughout the entire body. This discovery has shown that IL-6 is not only an exercise-induced factor, but that skeletal muscle is a secretory organ with endocrine functions. 

Although only 5% of myokines’ functions have been identified, this provides physicians and researchers with a new realm of cellular intelligence between skeletal muscle and the entire body. For example, exerkines, specifically released during exercise, may be released from skeletal muscle in the form of exosomes, which may contain genetic material in the form of mRNA and peptides that can influence cellular decision-making across the body. 

Although myokine research is being further researched and investigated, some of the major reactions that have been related to myokine stimulation have been stated below:

Myogenesis:

• Myokines such as myostatin influence muscular hypertrophy and increase fiber cross-sectional area. Exercise and physical activity can trigger the release of intramuscular signaling that induces growth factors. 

Muscle-Metabolic Communications

• IL-6 increases basal glucose uptake and glucose transporters, while also improving insulin-stimulated glucose uptake. Some studies have also shown that IL-6 improved intramyocellular and whole-body fatty acid oxidation.

Muscle-Brain Communications

•  Current research shows that brain-derived neurotrophic factor BDNF mRNA and BDNF are expressed in human muscle when exercise occurs, giving reason to believe that it is a valuable myokine to be studied, as it’s responsible for improving executive functions in the brain, such as cognition, memory, learning, and neurogenesis.

Muscle-Gastrointestinal Communications

• Myokines can affect appetite, lipolysis, and pancreatic beta-cell growth, as well as insulin regulation. One of the mechanisms by doing so is through IL-6 regulating apoptosis in beta-cells, preventing cellular death from metabolic stressors.

Muscle-Bone Communications

• Myostatin leads to an increase in bone mass and reduces bone destruction and osteoclast formation. 

Muscle-Vascular Communications

• Follistatin-like 1 (FSTL1) is produced in skeletal and cardiac muscle, which has given it the title of a cardiokine. This type of myokine promotes endothelial cell function and revascularization. This has been shown to improve substrate metabolism in animal models, while also having cardioprotective effects.

Muscle-Immune Communications

• During exercise the immune system is in full function. Lymphocytes and neutrophils rush to the blood, which is mediated by adrenaline. 

• IL-6 stimulates an anti-inflammatory environment to combat the low-grade inflammation from exercise and physical activity. IL-6 promotes anti-inflammatory cytokines to reduce inflammation in combination with cortisol and adrenaline

It’s necessary to continue this research into the realm of myokines and their vast endocrine responses throughout the body. Although it’s uncertain if all myokines are stimulated through physical activity, exercise, at rest, or through thermogenic effects, it’s clear that the potential benefits of understanding cellular signaling may have direct impacts on the clinical welfare of patients. 

There are recent signs that a muscle-brain endocrine loop exists due to the direct stimulation of myokine responses, like BDNF, which is responsible for neurogenesis and central nervous system functions.. Furthermore, the implications of muscle-stimulated IL-6 show improved regulation of glucose uptake and improved insulin regulation. In a study that depleted mice of IL-6, they not only gained weight and became obese, and developed insulin resistance. Furthermore, the ability of myokines to combat inflammation through immune system communications is explicitly important, due to the rise of chronic diseases that are caused by chronic inflammation. 

More research is being focused on integrated physiology and topics that target myokine discovery because of the vast effects that are seen from their production and release systemically. With that being said, it should also call public health attention as physical activity is declining and should be a topic of concern for the public and clinicians. 

References

Muscle–Organ Crosstalk: The Emerging Roles of Myokines

https://academic.oup.com/edrv/article/41/4/594/5835999