Potential role of irisin-mediated oxidative stress defense in systemic diseases
- 1Department of Cardiology, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, China
- 2Department of Respiratory Medicine, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, China
Abstract
Oxidative stress arises when excessive reactive oxygen species (ROS) overwhelm endogenous antioxidant defenses, leading to deleterious modifications of lipids, proteins, and DNA. Persistent oxidative stress is implicated in the pathogenesis of numerous chronic disorders, including cardiovascular diseases, neurodegenerative conditions, type 2 diabetes mellitus, and ischaemia–reperfusion (I/R) injury across multiple organs. Irisin, a myokine/adipokine proteolytically cleaved from fibronectin type III domain-containing protein 5 (FNDC5), was first characterized in 2012. Preclinical studies have increasingly demonstrated that irisin possesses potent antioxidant properties and exerts cytoprotective effects in diverse tissues. These antioxidant actions are mediated through multiple molecular mechanisms: activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway with subsequent upregulation of cytoprotective enzymes such as haem oxygenase-1 (HO-1); sirtuin 3 (SIRT3)-dependent deacetylation and activation of mitochondrial superoxide dismutase 2 (SOD2); inhibition of pro-oxidant enzymes including NADPH oxidase (NOX); and modulation of mitochondrial fusion-fission dynamics to preserve mitochondrial homeostasis. Functionally, irisin initiates intracellular signalling cascades, including AMP-activated protein kinase (AMPK), PI3K/Akt, and MAPK pathways, primarily through binding to cell-surface integrin αV receptors. This review systematically summarizes the molecular mechanisms underlying irisin-mediated antioxidation, delineates its organ-protective roles in cardiovascular, neurological, metabolic, hepatic, renal, pulmonary, gastrointestinal, skeletal, reproductive systems, as well as in sepsis and ageing, and discusses its translational potential as a clinical biomarker and therapeutic target for oxidative-stress-associated diseases.
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BibTeX
@article{xiao2026potential,
title = {{Potential role of irisin-mediated oxidative stress defense in systemic diseases}},
author = {Xue Xiao and Liying Wu and Xiaoming Zhu and Jie Zhou},
journal = {Frontiers in Cell and Developmental Biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1996659},
url = {https://doi.org/10.3389/fcell.2026.1996659},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Potential role of irisin-mediated oxidative stress defense in systemic diseases
AU - Xue Xiao
AU - Liying Wu
AU - Xiaoming Zhu
AU - Jie Zhou
PY - 2026
DA - 2026/10/13
JO - Frontiers in Cell and Developmental Biology
DO - 10.3389/fcell.2026.1996659
UR - https://doi.org/10.3389/fcell.2026.1996659
AB - Oxidative stress arises when excessive reactive oxygen species (ROS) overwhelm endogenous antioxidant defenses, leading to deleterious modifications of lipids, proteins, and DNA. Persistent oxidative stress is implicated in the pathogenesis of numerous chronic disorders, including cardiovascular diseases, neurodegenerative conditions, type 2 diabetes mellitus, and ischaemia–reperfusion (I/R) injury across multiple organs. Irisin, a myokine/adipokine proteolytically cleaved from fibronectin type III domain-containing protein 5 (FNDC5), was first characterized in 2012. Preclinical studies have increasingly demonstrated that irisin possesses potent antioxidant properties and exerts cytoprotective effects in diverse tissues. These antioxidant actions are mediated through multiple molecular mechanisms: activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway with subsequent upregulation of cytoprotective enzymes such as haem oxygenase-1 (HO-1); sirtuin 3 (SIRT3)-dependent deacetylation and activation of mitochondrial superoxide dismutase 2 (SOD2); inhibition of pro-oxidant enzymes including NADPH oxidase (NOX); and modulation of mitochondrial fusion-fission dynamics to preserve mitochondrial homeostasis. Functionally, irisin initiates intracellular signalling cascades, including AMP-activated protein kinase (AMPK), PI3K/Akt, and MAPK pathways, primarily through binding to cell-surface integrin αV receptors. This review systematically summarizes the molecular mechanisms underlying irisin-mediated antioxidation, delineates its organ-protective roles in cardiovascular, neurological, metabolic, hepatic, renal, pulmonary, gastrointestinal, skeletal, reproductive systems, as well as in sepsis and ageing, and discusses its translational potential as a clinical biomarker and therapeutic target for oxidative-stress-associated diseases.
SN - 2296-634X
ER -