Role of myokines in exercise and metabolism

Abstract

During the past 20 yr, it has been well documented that exercise has a profound effect on the immune system. With the discovery that exercise provokes an increase in a number of cytokines, a possible link between skeletal muscle contractile activity and immune changes was established. For most of the last century, researchers sought a link between muscle contraction and humoral changes in the form of an "exercise factor," which could mediate some of the exercise-induced metabolic changes in other organs such as the liver and the adipose tissue. We suggest that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either paracrine or endocrine effects should be classified as "myokines." Since the discovery of interleukin (IL)-6 release from contracting skeletal muscle, evidence has accumulated that supports an effect of IL-6 on metabolism. We suggested that muscle-derived IL-6 fulfils the criteria of an exercise factor and that such classes of cytokines should be named "myokines." Interestingly, recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. Thus skeletal muscle has the capacity to express several myokines. To date the list includes IL-6, IL-8, and IL-15, and contractile activity plays a role in regulating the expression of these cytokines in skeletal muscle. The present review focuses on muscle-derived cytokines, their regulation by exercise, and their possible roles in metabolism and skeletal muscle function and it discusses which cytokines should be classified as true myokines.

Myokines in insulin resistance and type 2 diabetes

“…Myokines and anti-inflammatory effects IL-6 is acutely increased in the circulation in response to exercise [79] and patients with insulin resistance, obesity and type 2 diabetes display chronically elevated serum levels of IL-6 [80][81][82]. An important source of circulating IL-6 in obesity is the expanding visceral adipose tissue mass.…”

“…After very intensive exercise such as marathon running, TNFα and IL-1β levels increase in response to muscle damage [79,90,91]. It is well established that muscle repair and regeneration after acute muscle injury involves tissue remodelling and growth-promoting local inflammation.…”

Skeletal muscle cells: from local inflammatory response to active immunity

“…36,37 The list of these exercise factors, named 'myokines' , includes IL-6, IL-8 and IL-15. However, the autocrine and in vivo paracrine effects of immunological active molecules, released by myofibres following a local inflammatory injury, are the main interest of this review.…”

Exercise and the microbiota

“…7 However, the anti-inflammatory effect of regular exercise and modulation of infection risk has been the subject of much research. 8 Of late, exercise's ability to enable cross talk between skeletal muscle and multiple other organs (e.g. brain, bone, liver, adipose tissue, gut) has become increasingly recognized.…”