Irisin protects mitochondria function during pulmonary ischemia/reperfusion injury

Abstract

Limb remote ischemic preconditioning (RIPC) is an effective means of protection against ischemia/reperfusion (IR)–induced injury to multiple organs. Many studies are focused on identifying endocrine mechanisms that underlie the cross-talk between muscle and RIPC-mediated organ protection. We report that RIPC releases irisin, a myokine derived from the extracellular portion of fibronectin domain–containing 5 protein (FNDC5) in skeletal muscle, to protect against injury to the lung. Human patients with neonatal respiratory distress syndrome show reduced concentrations of irisin in the serum and increased irisin concentrations in the bronchoalveolar lavage fluid, suggesting transfer of irisin from circulation to the lung under physiologic stress. In mice, application of brief periods of ischemia preconditioning stimulates release of irisin into circulation and transfer of irisin to the lung subjected to IR injury. Irisin, via lipid raft–mediated endocytosis, enters alveolar cells and targets mitochondria. Interaction between irisin and mitochondrial uncoupling protein 2 (UCP2) allows for prevention of IR-induced oxidative stress and preservation of mitochondrial function. Animal model studies show that intravenous administration of exogenous irisin protects against IR-induced injury to the lung via improvement of mitochondrial function, whereas in UCP2-deficient mice or in the presence of a UCP2 inhibitor, the protective effect of irisin is compromised. These results demonstrate that irisin is a myokine that facilitates RIPC-mediated lung protection. Targeting the action of irisin in mitochondria presents a potential therapeutic intervention for pulmonary IR injury.

Irisin alleviates liver ischemia-reperfusion injury by inhibiting excessive mitochondrial fission, promoting mitochondrial biogenesis and decreasing oxidative stress

“…Subsequent studies have shown that irisin could reduce oxidative/nitrative stress and protect endothelial cells in type 2 diabetes [12] . Additionally, irisin plays an important role in limb remote ischemic preconditioning (RIPC)-mediated lung protection via improvement of mitochondrial function [13] . However, the role of irisin in hepatic I/R injury remained unknown.…”

Uncoupling Protein 2 in Cardiovascular Health and Disease

“…In neurons, UCP2 upregulation under hypoxia is accompanied by histone deacetylation at H4K16Ac, and upregulation of SIRT1 ( Dmitriev and Papkovsky, 2015 ). Skeletal muscle ischemia induces myokine irisin which upregulates UCP2 expression in the lung against oxidative stress induced by ischemic injury ( Chen et al, 2017 ). Similarly, in endothelial cells, UCP2 is upregulated by SIRT1 mediated deacetylation ( Olmos et al, 2013 ), unlike in pancreas SIRT1 downregulates UCP2 expression ( Bordone et al, 2006 ).…”

FNDC5 alleviates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity via activating AKT

“…Except for the beneficial role in metabolic disorders, recent studies also implicated that FNDC5/Irisin was involved in regulating various cardiovascular diseases, such as atherosclerosis, hypertension, myocardial ischemia/reperfusion injury, and cardiac hypertrophy [21][22][23][24]. Besides, numerous researches verified that FNDC5 overexpression or irisin supplementation could preserve mitochondrial function and attenuate oxidative damage as well as cell apoptosis [25,26]. Based on these findings, we hypothesized that FNDC5/Irisin may be a promising candidate for the treatment of DOXinduced cardiotoxicity.…”