Irisin: An anti-inflammatory exerkine in aging and redox-mediated comorbidities

Abstract

Human beings lead largely sedentary lives. From an evolutionary perspective, such lifestyle is not beneficial to health. Exercise can promote many enabling pathways, particularly through circulating exerkines, to optimize individual health and quality of life. Such benefits might explain the protective effects of exercise against aging and noncommunicable diseases. Nevertheless, the miRNA-mediated molecular mechanisms and exerkine interorgan crosstalk that underlie the beneficial effects of exercise remain poorly understood. In this mini review, we focused on the exerkine, irisin, mainly produced by muscle contraction during adaptation to exercise and its beneficial effects on body homeostasis. Herein, the complex role of irisin in metabolism and inflammation is described, including its subsequent effects on thermogenesis through browning to control obesity and improve glycemic regulation for diabetes mellitus control, its potential to improve cognitive function (via brain derived neurotrophic factor), and its pathways of action and role in aging.

Keywords: exercise; exerkines; inflammaging; myokines; oxidative stress; skeletal muscle.

Figure 1

The exercise stimulates the peroxisome proliferator-activated receptor gamma coactivator 1 (PCG1)-alpha transcription, which in turn drives the expression of fibronectin type III domain-containing protein 5 (FNDC5), a membrane protein that is cleaved and secreted as irisin. Irisin acts on various human organs and tissues; which together orchestrate whole-body metabolism by regulating bone remodeling, "browning" of mature white adipocytes in response to exercise, glucose metabolism and insulin sensitivity in skeletal muscle, neuroplasticity, insulin sensitivity, and improving hepatic glucose and lipid metabolism. Irisin improves redox balance and inflammation. ATP, adenosine triphosphate; AMPK, AMP-activated protein kinase; ANGPTL4, angiopoietin-like 4; BDNF, brain derived neurotrophic factor; MCP-1, monocyte chemoattractant protein-1; FGF21, fibroblast growth factor 21; LIF, leukemia inhibitory factor; Metrnl, meteorin-like protein; SPARC, secreted protein acidic and cysteine-rich; ROS, reactive oxygen species; RNS, reactive nitrogen species; SOD, dismutase superoxide; GSH-PX, glutathione peroxidase and CAT-9, catalase.

Figure 2

Irisin secreted by skeletal muscle during the exercise reaches blood circulation and in general ameliorates the mitochondrial biogenesis, angiogenesis, endothelial cell proliferation and browning. Such benefits might explain the protective effects of exercise against type-2 Diabetes Mellitus, inflammation, oxidative stress and neurodegenerative disease. PGC1-α, peroxisome proliferator-activated receptor gamma coactivator 1 alpha; FNDC5', fibronectin type III domain-containing protein 5; TLR4, toll-like receptor 4; MyD88, myeloid differentiation primary response 88; HO-1, heme oxygenase-1; SOD, dismutase superoxide; GSH-Px, peroxidase glutathione; CAT-9, catalase; H202, oxygen peroxide; BDNF, brain-derived neurotrophic factor and NF-kB, factor nuclear kappa B.