Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6

Abstract

Skeletal muscle has recently been identified as an endocrine organ. It has, therefore, been suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert paracrine, autocrine, or endocrine effects should be classified as “myokines.” Recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. However, the first identified and most studied myokine is the gp130 receptor cytokine interleukin-6 (IL-6). IL-6 was discovered as a myokine because of the observation that it increases up to 100-fold in the circulation during physical exercise. Identification of IL-6 production by skeletal muscle during physical activity generated renewed interest in the metabolic role of IL-6 because it created a paradox. On one hand, IL-6 is markedly produced and released in the postexercise period when insulin action is enhanced but, on the other hand, IL-6 has been associated with obesity and reduced insulin action. This review focuses on the myokine IL-6, its regulation by exercise, its signaling pathways in skeletal muscle, and its role in metabolism in both health and disease.

Effect of resistance training on C-reactive protein, blood glucose and lipid profile in older women with differing levels of RT experience

“…These findings suggest that factors other than body composition changes are responsible for CRP decreases in those with RT experience. The greater reductions in CRP observed in the advanced group may be related to the amount of muscle mass involved in the contractile activity (Pedersen and Febbraio 2008). Moreover, myokines are sensitive to exercise intensity (Pedersen and Febbraio 2008), and although the trained and the novice participants performed the exercise at the same relative intensity, the advanced group achieved higher absolute workloads.…”

“…The greater reductions in CRP observed in the advanced group may be related to the amount of muscle mass involved in the contractile activity (Pedersen and Febbraio 2008). Moreover, myokines are sensitive to exercise intensity (Pedersen and Febbraio 2008), and although the trained and the novice participants performed the exercise at the same relative intensity, the advanced group achieved higher absolute workloads. Another metabolic profile variable that showed different adaptive responses between advanced and novice was the TC, in which only the beginner group reduced their values after the 8-week intervention period.…”

“…Muscle contraction produces myokines that have anti-inflammatory effects antagonizing the pro-inflammatory cytokines, thus favoring a reduction in inflammation and CRP (Pedersen and Febbraio 2008). Moreover, changes in some body composition components, such as body fat and skeletal muscle mass may play an important role for the reductions in inflammatory levels (Buresh and Berg 2014;Calle and Fernandez 2010;Donges et al 2010;Lee et al 2015;Mavros et al 2014;Selvin et al 2007), and RT has a positive impact on both of these outcomes.…”

“…In addition, training status may play an important role in metabolic and inflammatory adaptations induced by RT (Calle and Fernandez 2010;Pedersen and Febbraio 2008). Compared to novice trainees, subjects previously exposed to RT have a greater skeletal muscle mass, which is the primary metabolic target tissue for glucose (GLU) and triglycerides metabolism (Strasser and Schobersberger 2011) and acts as an endocrine organ releasing myokines with anti-inflammatory properties (Pedersen and Febbraio 2008).…”

Mechanism-Based Therapeutic Approaches to Cachexia

“…Skeletal muscle is a very heterogeneous tissue, in charge of several biological functions such as movement, stability, heat production and cold tolerance. Considered in the past as a mere protein reservoir, it is now recognized to release cytokines and other humoral factors (Pedersen & Febbraio, 2008). Since the skeletal muscle plays a pivotal role in the overall energy balance, regulating lipid flux, plasma glucose storage, and insulin sensitivity, it participates in the control of whole body metabolism, also acting in concert with the adipose tissue.…”