Irisin: A New Code Uncover the Relationship of Skeletal Muscle and Cardiovascular Health During Exercise

Abstract

Exercise not only produces beneficial effects on muscle itself via various molecular pathways, but also mediates the interaction between muscles and other organs in an autocrine/paracrine manner through myokines, which plays a positive role in maintaining overall health. Irisin, an exercise-derived myokine, has been found involved in the regulation of some cardiovascular diseases. However, the relationship between irisin and cardiovascular health is not fully elucidated and there are some divergences on the regulation of irisin by exercise. In this review, we present the current knowledge on the origin and physiology of irisin, describe the regulation of irisin by acute and chronic exercises, and discuss the divergences of the related research results. Importantly, we discuss the role of irisin as a biomarker in the diagnosis of cardiovascular diseases and describe its treatment and molecular mechanism in some cardiovascular diseases. It is expected that irisin will be used as a therapeutic agent to combat cardiovascular diseases or other disorders caused by inactivity in the near future.

Keywords: cardiovascular health; exercise; irisin; myokine; skeletal muscle.

Figure 1

Exercise induces increase of PCG1a expression in skeletal muscle, which in turn drives the production of membrane protein fibronectin type III domain-containing protein 5 (FNDC5). The FNDC5 is cleaved and secretes irisin (blue ball). Irisin enters in the blood circulation and participates in the metabolic regulation of lipid and glucose in some organs such as skeletal muscle, liver, and adipose tissue.

Figure 2

After irisin binds to membrane receptors, AMPK phosphorylation increase, and its downstream Akt/eNOS and Akt/mTOR signaling cascades are activated, thereby promoting NO secretion, autophagy, and angiogenesis, and inhibiting apoptosis and ROS production. On the other hand, irisin can also inhibit the secretion of pro-inflammatory factors by inhibiting p38 MAPK signaling pathway, and promote angiogenesis and cell proliferation, and inhibit apoptosis by activating ERK signaling pathway.

Figure 3

After secreted by skeletal muscle during exercise, irisin reaches cardiomyocytes and vascular endothelial cells via blood circulation (blue line). Irisin can promote angiogenesis, autophagy, and endothelial cell proliferation, improve mitochondrial function, inhibit cellular redox stress, apoptosis, inflammation, and endothelial dysfunction, and then play a key role in improving hypertension, myocardial infarction, atherosclerosis, and vascular inflammation.