Interleukin-6 as an adipokine and myokine: the regulatory role of cytokine in adipose tissue and skeletal muscle metabolism

Abstract

Purpose. Interleukin-6 (IL-6) belongs to the IL-6-type cytokine family, which, besides IL-6, comprises of IL-11, leukemia inhibitory factor (LIF), oncostatin M (OsM), ciliary neurotrophic factor (cNTF), cardiotrophin-1 (cT) and cardiotrophin-like cytokine (cLc). The metabolic effects of IL-6 differ markedly depending on the nature of the target cell with positive action on nerve cells' differentiation and hematopoesis, but negative in the etiology of autoimmune disease such as rheumatoid arthritis. In a target cell, IL-6 can simultaneously generate functionally distinct or sometimes contradictory signals depending on the in vivo environment, and the final physiological effect is a consequence of the orchestration of the diverse signals. Thus, its physiological effects are characterized by pleiotropy and redundancy. At present, it has been well documented that in obese individuals, IL-6, as an adipokine secreted into circulation by adipose tissue in proportion to body fat content and an elevated level of the cytokine in the plasma, adversely affects insulin signaling and glucose disposal in skeletal muscles and liver. Moreover, several lines of evidence indicated that IL-6 is a myokine synthesized in skeletal muscle and secreted into the bloodstream in response to exercise. In this way muscular work has a potential to stimulate adipose tissue lipolysis and provides an energy to working muscle. Furthermore, muscle-originated IL-6 acts locally, positively affecting intramuscular fat utilization. It has also been postulated that IL-6 is inevitable for satellite cell stimulation and muscle hypertrophy and repair.

Exercise Induced Adipokine Changes and the Metabolic Syndrome

“…IL-6 has both pro- and anti-inflammatory effects and is classified as an adipokine as well as a myokine and causes a wide range of sometimes contradictory effects. The physiologic nature of target cells and specific in vivo conditions are confounding factors in determining its final biological effect [ 126 ]. Indeed, IL-6 is a good example of a chemical that is able to cause cross talk amongst different tissues.…”