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FNDC5/Irisin Is Not Only a Myokine but Also an Adipokine
Open accessAbstract
Exercise provides clear beneficial effects for the prevention of numerous diseases. However, many of the molecular events responsible for the curative and protective role of exercise remain elusive. The recent discovery of FNDC5/irisin protein that is liberated by muscle tissue in response to exercise might be an important finding with regard to this unsolved mechanism. The most striking aspect of this myokine is its alleged capacity to drive brown-fat development of white fat and thermogenesis. However, the nature and secretion form of this new protein is controversial. The present study reveals that rat skeletal muscle secretes a 25 kDa form of FNDC5, while the 12 kDa/irisin theoretical peptide was not detected. More importantly, this study is the first to reveal that white adipose tissue (WAT) also secretes FNDC5; hence, it may also behave as an adipokine. Our data using rat adipose tissue explants secretomes proves that visceral adipose tissue (VAT), and especially subcutaneous adipose tissue (SAT), express and secrete FNDC5. We also show that short-term periods of endurance exercise training induced FNDC5 secretion by SAT and VAT. Moreover, we observed that WAT significantly reduced FNDC5 secretion in fasting animals. Interestingly, WAT of obese animals over-secreted this hormone, which might suggest a type of resistance. Because 72% of circulating FNDC5/irisin was previously attributed to muscle secretion, our findings suggest a muscle-adipose tissue crosstalk through a regulatory feedback mechanism.
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“However, it is important to note that irisin is not a protein exclusively secreted by muscle tissue.”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Roca-Rivada et al., 2013
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“He also found that both tissues secreted FNDC5/irisin under the stimulus of endurance training.”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Roca-Rivada et al., 2013
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“The study presented by Arturo Roca-Rivada et al. was a pioneer in showing that WAT also secretes FNDC5, the precursor of irisin, indicating that it is not only a myokine but also an adipokine (Roca-Rivada et al., 2013).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Roca-Rivada et al., 2013
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“Furthermore, the secretion of FNDC-5 is around 40% higher in slow-oxidative fibre-type muscle (i.e. soleus) than in fast-glycolytic fibre-type muscle (i.e. gastrocnemius) [47].”
In the citing paper
“Irisin is mainly secreted by skeletal muscle cells, although some secretion was also reported in WAT [204] and, to a lesser extent, in BAT [204,205].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [204]
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Cited by
Sorted by citations
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“Finally, irisin is an exercise-regulated myokine, which improves glucose tolerance [66] secreted by skeletal muscle [67] and adipose tissue [57] in response to exercise [68].”
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Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans
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“As irisin levels were higher in shivering subjects, we hypothesize muscle to be the main contributor to the observed irisin rise, although adiposederived irisin cannot be excluded (Roca-Rivada et al., 2013).”
Physiology and role of irisin in glucose homeostasis
Perakakis, N., Triantafyllou, G. A., Fernández-Real, J. M., Huh, J. Y., Park, K. H., Seufert, J., & Mantzoros, C. S. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.221 · Cited by 621
The myokine irisin increases cortical bone mass
Colaianni, G., Cuscito, C., Mongelli, T., Pignataro, P., Buccoliero, C., Liu, P., Lü, P., Sartini, L., Comite, M. D., Mori, G., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1516622112 · Cited by 521
“5A); this is in line with previous studies (21).”
Result
Metadata
- Authors
- Roca-Rivada, A., Castelao, C., Senin, L. L., Landrove, M. O., Baltar, J., Crujeiras, A. B., Seoane, L. M., Casanueva, F. F., & Pardo, M.
- Affiliations
- Instituto de Salud Carlos III (ES)
- Complejo Hospitalario Universitario de Santiago (ES)
- Corresponding author
- Pardo, María
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-04-11
- Volume
- 8
- Issue
- 4
- Pages
- e60563
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3623960
- OpenAlex
- W2008675205
- Cited by
- 612
- References
- 42
- Citations by year
- 2026: 12 · 2025: 35 · 2024: 45 · 2023: 46 · 2022: 51 · 2021: 65 · 2020: 45 · 2019: 42 · 2018: 44 · 2017: 52 · 2016: 55 · 2015: 56 · 2014: 44 · 2013: 19
- FWCI
- 40.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- RUNA. Repositorio Institucional del Sergas (Servicio Gallego de Salud (SERGAS)) (submittedVersion, cc-by)
- Funders
- Instituto de Salud Carlos III (CB06/03, FISP10/00537)
- Servicio Gallego de Salud
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Keywords
- FNDC5, irisin, adipokines, myokines, white adipose tissue, visceral adipose tissue, subcutaneous adipose tissue, skeletal muscle, endurance training, fasting, obesity, thermogenesis, secretome
- MeSH terms
- Animals, Fibronectins, Humans, Male, Physical Conditioning, Animal, Immunoblotting, Rats, Sprague-Dawley, Muscle, Skeletal, 3T3-L1 Cells, Mice, Rats, Adipose Tissue, White, Adipokines, Real-Time Polymerase Chain Reaction
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