FNDC5/Irisin: Physiology and Pathophysiology
Open accessAbstract
A sedentary lifestyle or lack of physical activity increases the risk of different diseases, including obesity, diabetes, heart diseases, certain types of cancers, and some neurological diseases. Physical exercise helps improve quality of life and reduces the risk of many diseases. Irisin, a hormone induced by exercise, is a fragmented product of FNDC5 (a cell membrane protein) and acts as a linkage between muscles and other tissues. Over the past decade, it has become clear that irisin is a molecular mimic of exercise and shows various beneficial effects, such as browning of adipocytes, modulation of metabolic processes, regulation of bone metabolism, and functioning of the nervous system. Irisin has a role in carcinogenesis; numerous studies have shown its impact on migration, invasion, and proliferation of cancer cells. The receptor of irisin is not completely known; however, in some tissues it probably acts via a specific class of integrin receptors. Here, we review research from the past decade that has identified irisin as a potential therapeutic agent in the prevention or treatment of various metabolic-related and other diseases. This article delineates structural and biochemical aspects of irisin and provides an insight into the role of irisin in different pathological conditions.
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Irisin is a myokine cleaved from FNDC5, a process regulated by PGC-1α during muscle contraction.
“Irisin is a myokine cleaved from the fibronectin type III domain-containing protein 5 (FNDC5), a process regulated by PGC-1α during muscle contraction [54].”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [54]
Endurance training appears to partially restore mitochondrial lipid composition, suggesting exercise is a compensatory strategy to preserve mitochondrial quality in context of myostatin deficiency.
“Importantly, endurance training appears to partially restore mitochondrial lipid composition, suggesting that exercise is a compensatory strategy to preserve mitochondrial quality in the context of myostatin deficiency [54].”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [54]
The Introduction discusses exercise-related myokines, and section 3.1 discusses mitochondrial function in adipose tissue, but neither addresses myostatin deficiency or restoration of mitochondrial lipid composition. Searches for endurance training, myostatin deficiency, and mitochondrial lipid composition found no passage supporting the attributed claim. Page numbers were unavailable in our copy. (LLM, conf=0.76)
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“Importantly, endurance training appears to partially restore mitochondrial lipid composition, suggesting that exercise is a compensatory strategy to preserve mitochondrial quality in the context of myostatin deficiency [54].”
Irisin enhances longevity by boosting SIRT1, AMPK, autophagy and telomerase
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- Authors
- Waseem, R., Shamsi, A., Mohammad, T., Hassan, M. I., Kazim, S. N., Chaudhary, A. A., Rudayni, H. A., Al-Zharani, M., Ahmad, F., & Islam, A.
- Affiliations
- Jamia Millia Islamia (IN)
- Imam Mohammad ibn Saud Islamic University (SA)
- Jamia Hamdard (IN)
- Corresponding author
- Islam, Asimul
- ORCID
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2022-02-08
- Volume
- 27
- Issue
- 3
- Pages
- 1118
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC8838669
- OpenAlex
- W4210977582
- Cited by
- 180
- References
- 77
- Citations by year
- 2026: 28 · 2025: 54 · 2024: 44 · 2023: 38 · 2022: 16
- FWCI
- 5.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Science and Engineering Research Board (CRG/2018/004641)
- Indian Council of Medical Research (ISRM/12/(127)/2020)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- irisin, FNDC5, physical activity, muscle-bone crosstalk, metabolic regulation, bone metabolism, nervous system function, cancer, integrins, therapeutic target, sedentary lifestyle, obesity, diabetes mellitus
- MeSH terms
- Animals, Fibronectins, Humans, Metabolic Diseases, Models, Molecular, Neoplasms, Protein Conformation, Signal Transduction, Exercise, Sedentary Behavior, Carcinogenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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