Definition
Irisin is a peptide hormone derived from proteolytic cleavage of the transmembrane protein fibronectin type III domain-containing protein 5 (FNDC5), primarily produced by skeletal muscle in response to exercise. PMID 33493316PMID 35872067PMID 41518679 It is considered an exerkine (specifically a myokine), as it is secreted during muscle contraction and mediates systemic effects of physical activity. PMID 40157803PMID 36843614
Biological function
Irisin's primary mechanism involves binding to the αV/β5 integrin receptor complex, activating signaling pathways that promote mitochondrial biogenesis, autophagy, and oxidative stress resistance. PMID 41518679 Its best-characterized function is inducing browning of white adipose tissue by increasing expression of uncoupling protein 1 (UCP1), thereby enhancing thermogenesis and energy expenditure. PMID 33493316PMID 35872067PMID 29608940 Beyond metabolic effects, irisin crosses the blood-brain barrier to induce brain-derived neurotrophic factor (BDNF) expression, supporting synaptic plasticity, neurogenesis, and cognitive function. PMID 40157803PMID 41518679PMID 36843614
Additional biological roles include maintaining glucose homeostasis, promoting bone remodeling through enhanced osteoblast differentiation, stimulating myogenesis in skeletal muscle, and exerting cardioprotective effects via SIRT1/PGC-1α upregulation. PMID 41518679PMID 36225200PMID 40886173
Exerkine classification
Irisin is classified as an exerkine because exercise activates PGC-1α in skeletal muscle, which stimulates FNDC5 production and subsequent irisin secretion. PMID 40157803PMID 36225200 Plasma irisin concentrations increase with acute exercise in an intensity-dependent manner, with levels remaining elevated for hours after prolonged intense exercise. PMID 40157803 This exercise-induced release and its role in mediating beneficial systemic effects of physical activity—including metabolic improvements, anti-inflammatory actions, and neuroprotection—firmly establish irisin as an exerkine. PMID 36843614PMID 35793739 While initially described as a myokine, irisin is also expressed in adipose and neural tissues, functioning through autocrine, paracrine, and endocrine mechanisms. PMID 41518679PMID 40886173
Therapeutic potential
Irisin is an exercise-induced myokine that exerts therapeutic effects through multiple mechanisms, including anti-inflammatory, anti-apoptotic, and anti-oxidative properties. PMID 29414191 It promotes browning of white adipose tissue, regulates glucose and lipid homeostasis, and activates signaling pathways that enhance mitochondrial biogenesis, autophagy, and oxidative stress resistance. PMID 29414191PMID 41518679
Metabolic diseases represent a major therapeutic target. Irisin improves β-cell function and insulin secretion in diabetes, alleviates obesity through thermogenesis and energy expenditure, and shows promise for treating nonalcoholic fatty liver disease and polycystic ovary syndrome. PMID 39532260PMID 28394923PMID 35793739PMID 29170905 In type 2 diabetes models, irisin significantly reduced body weight and blood glucose while improving glucose tolerance. PMID 28394923
Cardiovascular applications include ameliorating maladaptive cardiac hypertrophy and fibrosis, causing systemic vasodilation, and mitigating experimental heart failure through SIRT1/PGC-1α upregulation. PMID 40886173 Irisin reduces myocardial injury and protects against ischemia/reperfusion damage. PMID 39532260PMID 41452463
Neurodegenerative diseases benefit from irisin's ability to increase brain-derived neurotrophic factor in the hippocampus, reduce amyloid burden, limit α-synuclein pathology, and stabilize blood-brain barrier integrity. PMID 35872251PMID 41518679 Studies suggest protective effects in Alzheimer's disease, Parkinson's disease, and stroke. PMID 35793739PMID 35872251
Additional therapeutic targets include bone metabolism (positive association with bone mineral density and inverse association with osteoporotic fractures), cancer, sarcopenia, and various inflammatory conditions. PMID 29170905PMID 35793739PMID 36225200PMID 41518679PMID 29414191PMID 39532260 Irisin also demonstrates anxiolytic and antidepressant effects. PMID 35872251
The therapeutic mechanisms involve binding to integrin αV/β5 receptors and modulating programmed cell death pathways including apoptosis, ferroptosis, pyroptosis, and autophagy. PMID 41518679PMID 41452463
Evidence
PubMed and ClinicalTrials.gov, snapshot of February 2026. Counts are keyword-based and include every study that mentions Irisin. Compare across exerkines →
References 15
Primary literature cited in this profile. Each identifier opens the article on PubMed.