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Project description:Irisin regulated genes in mouse liver derived AML12 cells
| PRJNA971191 | ENA
Project description:Physical activity is thought to provide clinical benefit in Parkinson’s diseas (PD). Irisin is a blood-brain barrier permeable exercise-induced polypeptide secreted by muscle that mediates, in part, the beneficial effects of exercise. Here we show that irisin prevents pathologic -synuclein (-syn) induced neurodegeneration in the -syn preformed fibril mouse model of sporadic PD. Intravenous delivery of adenoviral irisin in vivo after the stereotaxic intrastriatal injection of -syn pre-formed fibrils reduced the formation of pathologic -syn and prevented the loss of dopamine neurons and reductions in striatal dopamine. Irisin also reduced the -syn pre-formed fibril induced motor deficits as assessed by the pole test and grip strength test. Administration of recombinant irisin in primary cortical neurons prevented pathologic -syn toxicity. Tandem mass spectrometry and biochemical analysis revealed that irisin reduced pathologic -syn by enhancing endolysosomal degradation of pathologic -syn. Our findings highlight the potential for therapeutic disease modification of irisin in PD.
2022-10-15 | PXD032670 | Pride
Project description:Irisin is a recently identified myokine that is induced by exercise and stimulates brown-fat-like development of white fat and energy expenditure in humans and mice. In this study, we aimed to evaluate the pro-proliferative effect of irisin on C2C12 myoblasts and its mechanisms of action.
2019-08-13 | E-MTAB-8180 | biostudies-arrayexpress
Project description:Identifying secreted mediators driving the cognitive benefits of exercise holds great promise for the treatment of cognitive decline in aging or Alzheimer’s disease (AD). Here, we show that irisin, the cleaved and circulating form of the exercise-induced membrane protein FNDC5, is sufficient to confer the exercise benefits on cognitive function. Genetic deletion of FNDC5/irisin (global F5KO mice) impairs cognitive function in exercise, aging, and AD. Diminished pattern separation in F5KOs can be rescued by delivering irisin directly into the dentate gyrus, suggesting that irisin is the active moiety. In F5KOs, adult-born neurons in the dentate gyrus are morphologically, transcriptionally, and functionally abnormal. Importantly, elevation of circulating irisin levels by peripheral administration, resulting in enrichment of central irisin, was sufficient to improve both the cognitive deficit and neuropathology in AD mouse models. Irisin is a crucial regulator of cognitive benefits of exercise and potential therapeutic for treating cognitive disorders including AD.
2021-08-11 | GSE179078 | GEO
Project description:Identifying secreted mediators driving the cognitive benefits of exercise holds great promise for the treatment of cognitive decline in aging or Alzheimer’s disease (AD). Here, we show that irisin, the cleaved and circulating form of the exercise-induced membrane protein FNDC5, is sufficient to confer the exercise benefits on cognitive function. Genetic deletion of FNDC5/irisin (global F5KO mice) impairs cognitive function in exercise, aging, and AD. Diminished pattern separation in F5KOs can be rescued by delivering irisin directly into the dentate gyrus, suggesting that irisin is the active moiety. In F5KOs, adult-born neurons in the dentate gyrus are morphologically, transcriptionally, and functionally abnormal. Importantly, elevation of circulating irisin levels by peripheral administration, resulting in enrichment of central irisin, was sufficient to improve both the cognitive deficit and neuropathology in AD mouse models. Irisin is a crucial regulator of cognitive benefits of exercise and potential therapeutic for treating cognitive disorders including AD.
2021-08-11 | GSE174210 | GEO
Project description:Identifying secreted mediators driving the cognitive benefits of exercise holds great promise for the treatment of cognitive decline in aging or Alzheimer’s disease (AD). Here, we show that irisin, the cleaved and circulating form of the exercise-induced membrane protein FNDC5, is sufficient to confer the exercise benefits on cognitive function. Genetic deletion of FNDC5/irisin (global F5KO mice) impairs cognitive function in exercise, aging, and AD. Diminished pattern separation in F5KOs can be rescued by delivering irisin directly into the dentate gyrus, suggesting that irisin is the active moiety. In F5KOs, adult-born neurons in the dentate gyrus are morphologically, transcriptionally, and functionally abnormal. Importantly, elevation of circulating irisin levels by peripheral administration, resulting in enrichment of central irisin, was sufficient to improve both the cognitive deficit and neuropathology in AD mouse models. Irisin is a crucial regulator of cognitive benefits of exercise and potential therapeutic for treating cognitive disorders including AD.
2021-08-11 | GSE174211 | GEO
Project description:A pathological hallmark of Alzheimer’s disease (AD) is the deposition of amyloid-β protein (Aβ) in the brain. Physical exercise has been shown to reduce Aβ burden in various AD mouse models, but the underlying mechanisms have not been elucidated. Irisin, an exercise-induced hormone, is the secreted form of fibronectin-domain III containing 5 (FNDC5). Here, using a three-dimensional (3D) cell culture model of AD, we show that irisin significantly reduces Aβ pathology by increasing astrocytic release of the Aβ-degrading enzyme neprilysin (NEP). This is mediated by downregulation of ERK-STAT3 signaling. Finally, we show that integrin αV/β5 acts as the irisin receptor on astrocytes required for irisin-induced release of astrocytic NEP, leading to clearance of Aβ. Our findings reveal for the first time a cellular and molecular mechanism by which exercise-induced irisin attenuates Aβ pathology, suggesting a new target pathway for therapies aimed at the prevention and treatment of AD
2023-09-08 | GSE240161 | GEO
Project description:Irisin is secreted by muscle, increased with exercise, and conveys certain physiological benefits. Earlier studies showed that short-term irisin treatment caused browning of subcutaneous adipose tissue (SAT) in mice, with improved glucose tolerance; the effects of more chronic irisin treatment and mechanisms at play have not been explored. We demonstrate here that chronic irisin application improves obesity and dramatically reduces glucose intolerance. This treatment increases an IL-33+ mesenchymal stromal cell (mSC) population in visceral fat tissue while genetic ablation of irisin reduces plasma IL-33 levels and decreases thermogenic gene expression in SAT. Importantly, irisin directly induces IL-33 expression in mSCs and preserves ST2+ regulatory T (Treg) cells. Inhibition of IL-33 blunts these irisin-mediated effects on energy expenditure and glucose homeostasis, largely through IL33-mediated regulation of ST2+ Treg cells. These data indicate that irisin improves obesity and glucose intolerance, with no muscle loss, through a key immunomodulatory pathway in obese mice.
2025-12-05 | GSE283234 | GEO
Project description:Collectively, our study reveals that irisin can enhance chondrogenic differentiation of hMSCs via the Rap1/PI3K/AKT pathway, suggesting that irisin possesses prospects in cartilage regeneration. Collectively, our study reveals that irisin can enhance chondrogenic differentiation of hMSCs via the Rap1/PI3K/AKT pathway, suggesting that irisin possesses prospects in cartilage regeneration.
2022-05-10 | GSE201594 | GEO
Project description:Exercise benefits the human body in many ways. Irisin is secreted by muscle, increased with exercise, and conveys many physiological benefits, including improved cognition and resistance to neurodegeneration. Irisin acts via αV integrins; however, a mechanistic understanding of how small polypeptides like irisin can signal through integrins is poorly understood. Using mass spectrometry and cryo-EM, we demonstrate that extracellular heat-shock protein 90α (eHsp90α) is secreted by muscle with exercise and acts as a required cofactor that “opens” the integrin αVβ5 structure to allows for high affinity irisin binding and signaling through an eHsp90α/αV/β5 complex. By including hydrogen/deuterium exchange data, we generate and experimentally validate a 2.98 Å RMSD irisin/αVβ5 complex docking model. Irisin binds very tightly to an alternative interface on αVβ5 distinct from that involved in its interaction with known ligands. These data together elucidate a non-canonical mechanism by which a small polypeptide hormone like irisin can function through integrins.
2023-06-04 | PXD035397 | Pride