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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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Pathophysiology of type 2 diabetes mellitus
Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K. B., Ostolaza, H., & Martín, C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176275 · Cited by 3,360
“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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Park, K., Zaichenko, L., Brinkoetter, M. T., Thakkar, B., Sahin-Efe, A., Joung, K. E., Tsoukas, M. A., Geladari, E. V., Huh, J. Y., Dincer, F., et al. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2373 · Cited by 513
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“However, a few recent studies observed positive associations of muscle Fndc5 with insulin resistance (Huh et al. 2012; Roca-Rivada et al. 2013; Stengel et al. 2013), speculating on the negative, desensitizing effects of irisin on insulin action.”
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Irisin – a myth rather than an exercise-inducible myokine
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“[21] Roca-Rivada A, Castelao C, Senin LL, Landrove MO, Baltar J, Belen Crujeiras A, et al.”
Irisin: A Hope in Understanding and Managing Obesity and Metabolic Syndrome
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“Further, adipose tissue of human origin expresses and secretes FNDC5/irisin (103).”
BackgroundInfluentialAdipo-myokines: two sides of the same coin–mediators of inflammation and mediators of exercise
Raschke, S., & Eckel, J. (2013) · Mediators of Inflammation · doi:10.1155/2013/320724 · Cited by 296
“Furthermore, to demonstrate the secretion of irisin from HEK293 cells and to analyze murine and human serum samples, the authors used an antibody, which most likely cannot detect the cleaved irisin, since the antibody used is directed against the C-terminal part of the protein (Abcam 149–178, Cterminal) [58].”
BackgroundPekkala, S., Wiklund, P. K., Hulmi, J. J., Ahtiainen, J. P., Horttanainen, M., Pöllänen, E., Mäkelä, K. A., Kainulainen, H., Häkkinen, K., Nyman, K., et al. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2013.263707 · Cited by 292
“Yet, the latest reports showed that skeletal muscle FNDC5 expression and circulating irisin levels were decreased in obese patients and associated with insulin sensitivity, and that adipose tissue might secrete irisin in response to exercise (Moreno-Navarrete et al. 2013; Roca-Rivada et al. 2013).”
BackgroundRodríguez, A., Ezquerro, S., Méndez-Giménez, L., Becerril, S., & Frühbeck, G. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00297.2015 · Cited by 287
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“This myokine is a transmembrane protein expressed principally in skeletal muscle (100), but is also expressed in WAT to a lower extent (101).”
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Three new players in energy regulation: Preptin, adropin and irisin
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Progress and Challenges in the Biology of FNDC5 and Irisin
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“FNDC5 32-212 20 300 28 000 25 000** 23 – 28 000 (14, 17-20)”
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“Interestingly, recent reports have suggested that irisin is not only a myokine but also an adipokine, although expressed to a lesser extent (Moreno- Navarrete et al. 2013; Roca-Rivada et al. 2013).”
BackgroundThe Structure of Irisin Reveals a Novel Intersubunit β-Sheet Fibronectin Type III (FNIII) Dimer
Schumacher, M. A., Chinnam, N. B., Ohashi, T., Shah, R., & Erickson, H. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.516641 · Cited by 244
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“Other evidences suggest that it is also secreted by adipose tissue, hence IR could be defined an adipomyokine (Roca-Rivada et al., 2013).”
Pardo, M., Crujeiras, A. B., Amil, M., Agüera, Z., Jiménez‐Múrcia, S., Baños, R., Botella, C., de la Torre, R., Estivill, X., Fagundo, A. B., et al. (2014) · International Journal of Endocrinology · doi:10.1155/2014/857270 · Cited by 219
“This effect may improve the WAT metabolic profile and enhance whole-body energy expenditure, making irisin a potential new target for the treatment of metabolic diseases.”
BackgroundMethodInfluentialSerum Irisin Levels Are Regulated by Acute Strenuous Exercise
Löffler, D., Müller, U., Scheuermann, K., Friebe, D., Gesing, J. K., Bielitz, J., Erbs, S., Landgraf, K., Wagner, I. V., Kieß, W., et al. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-2932 · Cited by 222
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“,(5) where the stained bands were diffuse as expected for heavy glycosylation, the 25 kDa bands in RocaRivada et al.(10) are sharp.”
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“Irisin secretion from scWAT and vWAT was induced by short-term periods of endurance exercise training, whereas it was decreased by long-term exercise training and fasting [250,251].”
BackgroundResistance exercise induces a greater irisin response than endurance exercise
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“Irisin was also found to be secreted by adipocytes in a rat [12,13] or mouse model, as well as by human adipose tissue [14].”
BackgroundBrowning of white adipose tissue: lessons from experimental models
Bargut, T. C. L., Souza‐Mello, V., Águila, M. B., & Mandarim‐de‐Lacerda, C. A. (2017) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2016-0051 · Cited by 212
“Also, irisin acts via PGC1-α to enhance UCP1 expression, which is also a PPAR-α target gene, maximizing thermogenesis [39, 40].”
BackgroundIrisin exerts dual effects on browning and adipogenesis of human white adipocytes
Zhang, Y., Xie, C., Wang, H., Foss, R. M., Clare, M., George, E. V., Li, S., Katz, A. J., Cheng, H., Ding, Y., et al. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00094.2016 · Cited by 197
“Interestingly, since WAT produces irisin (36), circulating irisin levels may be lower than the local irisin concentration due to paracrine and autocrine regulation.”
BackgroundCrosstalk between adipokines and myokines in fat browning
Rodríguez, A., Becerril, S., Ezquerro, S., Méndez-Giménez, L., & Frühbeck, G. (2016) · Acta Physiologica · doi:10.1111/apha.12686 · Cited by 196
“The adipose tissue not only constitutes a target for irisin, but also expressed the FNDC5 gene and secretes irisin, but to a lesser extent than the skeletal muscle (Moreno-Navarrete et al. 2013, Roca-Rivada et al. 2013).”
BackgroundSarcopenia – The search for emerging biomarkers
Kalinkovich, A., & Livshits, G. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.05.001 · Cited by 191
“Data collected soon after its discovery confirmed the ability of irisin to be released after physical activity (Huh et al., 2012; Roca-Rivada et al., 2013), suggesting its role as a potential mediator of the health-promoting effects of physical exercise.”
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“However, it has recently been reported that irisin is also produced by adipocytes (2, 6), whereas circulating irisin was found to be increased in insulin resistance states and metabolic syndrome (9, 10).”
BackgroundInfluentialWu, M. V., Bikopoulos, G. J., Hung, S., & Ceddia, R. B. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.591008 · Cited by 187
Inter‐organ communication: a gatekeeper for metabolic health
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“Some groups have suggested that irisin can also be produced and secreted by adipose tissue and liver [120].”
New insights into the cellular activities of Fndc5/Irisin and its signaling pathways
Rabiee, F., Lachinani, L., Ghaedi, S., Nasr‐Esfahani, M. H., Megraw, T. L., & Ghaedi, K. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00413-3 · Cited by 188
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“, skeletal myocytes, adipocytes, cardiomyocytes and purkinje cells of cerebellum) for irisin production exist (Roca-Rivada et al. 2013; Raschke and Eckel 2013; Dun et al. 2013) and interactions with other cytokines and hormones (e.”
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“Recent studies have shown that irisin may also act as an adipokine (21, 25) as well as a potential “neurokine” (9, 12).”
BackgroundIrisin as a Multifunctional Protein: Implications for Health and Certain Diseases
Korta, P., Pocheć, E., & Mazur-Biały, A. I. (2019) · Medicina · doi:10.3390/medicina55080485 · Cited by 169
“The mass of FNDC5 proteins range from 20 to 32 kDa depending on the number and structure of oligosaccharides (glycans) attached to the protein molecule during the post-translational process of N-glycosylation [4,9].”
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Irisin, an exercise‐induced myokine as a metabolic regulator: an updated narrative review
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“…experimental study further illustrates this fact given that correlating FNDC5/ IRISIN mRNA levels with secretion levels was not evident in most of the conditions; which is coherent taking into account that irisin scission is proteolitically regulated by an unknown enzyme (Roca-Rivada et al., 2013).”
BackgroundResultInfluentialPhysical Exercise as Therapy for Type 2 Diabetes Mellitus: From Mechanism to Orientation
Yang, D., Yang, Y., Li, Y., & Han, R. (2019) · Annals of Nutrition and Metabolism · doi:10.1159/000500110 · Cited by 165
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“However, inamanner similar to leptin, irisin circulating concentration [51–53] as well as its expression in muscle and adipose tissue [20,54] is increased in obesity, which suggests potential irisin resistance [55] as occurs with leptin.”
BackgroundInfluentialMiyamoto-Mikami, E., Sato, K., Kurihara, T., Hasegawa, N., Fujie, S., Fujita, S., Sanada, K., Hamaoka, T., Tabata, I., & Iemitsu, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0120354 · Cited by 143
“FNDC5mRNA is expressed at higher levels in skeletal muscle than in other organs [9], and FNDC5 expression in skeletal muscle contributes significantly to circulating irisin levels [5, 9, 22].”
BackgroundRachid, T. L., Penna‐de‐Carvalho, A., Bringhenti, I., Águila, M. B., Mandarim‐de‐Lacerda, C. A., & Souza‐Mello, V. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.12.027 · Cited by 143
“The enhanced UCP-1 gene expression is positively correlated with irisin gene expression in our treated groups, given that this adipokine seems to induce thermogenesis via PPARalpha (Komatsu et al., 2010; Roca-Rivada et al., 2013).”
Multiple Roles in Neuroprotection for the Exercise Derived Myokine Irisin
Farshbaf, M. J., & Alviña, K. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.649929 · Cited by 150
“Further, Irisin could also be secreted from adipose tissue in addition to skeletal muscle (Roca-Rivada et al., 2013).”
BackgroundInfluentialChronic Exercise Training and Circulating Irisin in Adults: A Meta-Analysis
Qiu, S., Cai, X., Sun, Z., Schumann, U., Zügel, M., & Steinacker, J. M. (2015) · Sports Medicine · doi:10.1007/s40279-014-0293-4 · Cited by 129
“First, recent studies demonstrated that irisin is not only a myokine but also an adipokine that is released from adipose tissue [20, 21].”
BackgroundRodrı́guez, A., Becerril, S., Méndez-Giménez, L., Ramírez, B., Sáinź, N., Catalán, V., Gómez‐Ambrosi, J., & Frühbeck, G. (2014) · International Journal of Obesity · doi:10.1038/ijo.2014.166 · Cited by 130
Browning of white fat: does irisin play a role in humans?
Elsen, M., Raschke, S., & Eckel, J. (2014) · Journal of Endocrinology · doi:10.1530/joe-14-0189 · Cited by 130
“Furthermore, even a trend toward a decrease in Ucp1 mRNA expression in BAT has been observed in rats after 3 weeks of endurance exercise (Roca-Rivada et al. 2013).”
BackgroundMethodInfluentialEffects and underlying mechanisms of irisin on the proliferation and apoptosis of pancreatic β cells
Liu, S., Du, F., Li, X., Wang, M., Duan, R., Zhang, J., Wu, Y., & Zhang, Q. (2017) · PLoS ONE · doi:10.1371/journal.pone.0175498 · Cited by 135
Irisin Is Elevated in Skeletal Muscle and Serum of Mice Immediately after Acute Exercise
Brenmoehl, J., Albrecht, E., Komolka, K., Schering, L., Langhammer, M., Hoeflich, A., & Maak, S. (2014) · International Journal of Biological Sciences · doi:10.7150/ijbs.7972 · Cited by 131
“The positive effect of exercise on Fndc5 expression was confirmed in a number of studies at mRNA (11,15,18,24) and protein level (24,29) in different experimental settings in rats and humans.”
BackgroundInfluentialIrisin: a new molecular marker and target in metabolic disorder
Chen, J., Huang, Y., Gusdon, A. M., & Qu, S. (2015) · Lipids in Health and Disease · doi:10.1186/1476-511x-14-2 · Cited by 126
“[14] found secretion of irisin was higher from white adipose tissues of diet-induced obese rats compared to lean controls, suggesting that adipose tissue, especially in obesity, was an important source of irisin.”
BackgroundCirculating serum irisin levels in obesity and type 2 diabetes mellitus
Shoukry, A., Shalaby, S. M., Bdeer, S. E., Mahmoud, A. A., Mousa, M. M., & Khalifa, A. (2016) · IUBMB Life · doi:10.1002/iub.1511 · Cited by 125
“Current studies reported that irisin is not only secreted by muscle tissue and demonstrated that irisin is a new adipokine with an important autocrine and endocrine function (9).”
BackgroundInfluentialAydın, S., Aydın, S., Kuloğlu, T., Yılmaz, M., Kalayci, M., Sahin, İ., & Cicek, D. (2013) · Peptides · doi:10.1016/j.peptides.2013.09.011 · Cited by 118
Palermo, A., Strollo, R., Maddaloni, E., Tuccinardi, D., D’Onofrio, L., Briganti, S., Defeudis, G., Pascalis, M. D., Lazzaro, M. C., Colleluori, G., et al. (2014) · Clinical Endocrinology · doi:10.1111/cen.12672 · Cited by 118
Provatopoulou, X., Georgiou, G. P., Kalogera, E., Kalles, V., Matiatou, M., Papapanagiotou, I., Sagkriotis, A., Zografos, G., & Gounaris, A. (2015) · BMC Cancer · doi:10.1186/s12885-015-1898-1 · Cited by 123
“Interestingly, irisin has a different pattern of secretion depending on the anatomical location of adipose tissue, with subcutaneous adipose tissue secreting more protein than visceral adipose tissue [2].”
BackgroundNovelle, M. G., Contreras, C., Romero, A., López, M., & Diéguez, C. (2013) · International Journal of Endocrinology · doi:10.1155/2013/746281 · Cited by 122
“Another interesting feature, also reported by those authors, indicates that FNDC5/irisin has a secretion profile similar to other adipokines like leptin.”
BackgroundResultInfluentialTsai, C., Pan, C., Tseng, Y., Chen, F., Chang, Y.-C., & Wang, T.-C. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113472 · Cited by 123
Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2
Zhu, W., Sahar, N.-E., Javaid, H. M. A., Pak, E. S., Liang, G., Wang, Y., Ha, H., & Huh, J. Y. (2021) · Cells · doi:10.3390/cells10123306 · Cited by 119
“reported that under basal conditions, soleus muscle secretes approximately 40% more FNDC5/irisin than gastrocnemius muscle [49].”
BackgroundGamas, L., Matafome, P., & Seiça, R. (2015) · Journal of Diabetes Research · doi:10.1155/2015/359159 · Cited by 114
“Although many studies have described the effects of irisin on subcutaneous adipose tissue, at least a couple of studies have reported its browning-promoting effects of visceral adipose tissue [34, 35].”
BackgroundDasarathy, J., Periyalwar, P., Allampati, S., Bhinder, V., Hawkins, C., Brandt, P., Khiyami, A., McCullough, A. J., & Dasarathy, S. (2013) · Liver International · doi:10.1111/liv.12312 · Cited by 115
“Recent data on the regulatory role of skeletal muscle secreted protein, irisin on adipose tissue function (50, 51) as well as TGFb superfamily member, myostatin on insulin resistance (52, 53) suggest that these molecular abnormalities may play a contributory role in the development and progression of NAFLD.”
BackgroundRelationship between circulating irisin, renal function and body composition in type 2 diabetes
Liu, J., Liu, S., Wong, M. D. S., Tan, C. S. H., Subramaniam, T., Sum, C. F., & Lim, S. C. (2013) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2013.09.011 · Cited by 114
“Recent studies also suggest that irisin is not only a myokine but also a novel adipokine, although the contribution of adipose tissue to the abundance of circulating irisin remains unknown (MorenoNavarrete et al., 2013; Roca-Rivada et al., 2013).”
BackgroundCirculating irisin, omentin-1, and lipoprotein subparticles in adults at higher cardiovascular risk
Panagiotou, G., Mu, L., Na, B., Mukamal, K. J., & Mantzoros, C. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.06.001 · Cited by 113
“In addition, accumulating data support the production of irisin by adipocytes, suggesting its dual role as a myokine and adipokine [22, 40].”
BackgroundIrisin as a predictor of glucose metabolism in children: sexually dimorphic effects
Al‐Daghri, N. M., Alkharfy, K. M., Rahman, S., Amer, O. E., Vinodson, B., Sabico, S., Piya, M. K., Harte, A. L., McTernan, P. G., Alokail, M. S., et al. (2013) · European Journal of Clinical Investigation · doi:10.1111/eci.12196 · Cited by 110
Varela-Rodríguez, B. M., Pena-Bello, L., Juiz-Valiña, P., Bretal, B. V., Cordido, F., & Sangiao‐Alvarellos, S. (2016) · Scientific Reports · doi:10.1038/srep29898 · Cited by 115
Asadi, Y., Gorjipour, F., Behrouzifar, S., & Vakili, A. (2018) · Neurochemical Research · doi:10.1007/s11064-018-2569-9 · Cited by 109
An update on the role of irisin in the regulation of endocrine and metabolic functions
Mahgoub, M., D’Souza, C. M., Darmaki, R. S. A., Baniyas, M. M. Y. H., & Adeghate, E. A. (2018) · Peptides · doi:10.1016/j.peptides.2018.03.018 · Cited by 110
“Moreover, they have suggested that like other adipokines, irisin secretion from subcutaneous adipose tissues is affected by the circulating levels of irisin [113].”
The Role of Adipokines in Breast Cancer: Current Evidence and Perspectives
Christodoulatos, G. S., Spyrou, N., Kadillari, J., Psallida, S., & Dalamaga, Μ. (2019) · Current Obesity Reports · doi:10.1007/s13679-019-00364-y · Cited by 109
Aydın, S., Aydın, S., Kobat, M. A., Kalaycı, M. Z., Eren, M. N., Yılmaz, M., Kuloğlu, T., Gül, E., Seçen, Ö., Alataş, Ö. D., et al. (2014) · Peptides · doi:10.1016/j.peptides.2014.04.002 · Cited by 106
Irisin and Its Relation to Insulin Resistance and Puberty in Obese Children: A Longitudinal Analysis
Reinehr, T., Elfers, C., Lass, N., & Roth, C. L. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-1208 · Cited by 107
Crujeiras, A. B., Pardo, M., & Casanueva, F. F. (2014) · Clinical Endocrinology · doi:10.1111/cen.12627 · Cited by 104
Pahlavani, M., Razafimanjato, F., Ramalingam, L., Kalupahana, N. S., Moussa, H. M., Scoggin, S. O., & Moustaïd‐Moussa, N. (2016) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2016.08.012 · Cited by 102
“Irisin is another marker that has received significant attention but also some controversy as a myokine/adipokne which, upon exercise or cold exposure activates the browning and thermogenic program in WAT [54, 55].”
BackgroundMarcher, A.-B., Loft, A., Nielsen, R., Vihervaara, T., Madsen, J. G. S., Sysi‐Aho, M., Ekroos, K., & Mandrup, S. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.069 · Cited by 102
“Although Fndc5 is expressed to much lower levels in adipocytes comparedwithmuscle cells (Huh et al., 2012), subcutaneous WAT secretes significant levels of irisin, which is elevated during exercise (Roca-Rivada et al., 2013).”
BackgroundIrisin, a fascinating field in our times
Bao, J., She, Q.-Y., Hu, P., Jia, N., & Li, A. (2022) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2022.06.003 · Cited by 111
Irisin reduces inflammatory signaling pathways in inflammation-mediated metabolic syndrome
Slate‐Romano, J., Yano, N., & Zhao, T. C. (2022) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2022.111676 · Cited by 105
Thermogenic brown and beige/brite adipogenesis in humans
Cereijo, R., Giralt, M., & Villarroya, F. (2014) · Annals of Medicine · doi:10.3109/07853890.2014.952328 · Cited by 95
Ellefsen, S., Vikmoen, O., Slettaløkken, G., Whist, J. E., Nygaard, H., Hollan, I., Rauk, I., Vegge, G., Strand, T. A., Raastad, T., et al. (2014) · European Journal of Applied Physiology · doi:10.1007/s00421-014-2922-x · Cited by 91
Is irisin the new player in exercise-induced adaptations or not? A 2017 update
Fatouros, I. G. (2017) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2017-0674 · Cited by 95
“Studies suggest that irisin may not act on subcutaneous WAT, but it is rather related to browning at the level of visceral adipose tissue [112, 113].”
BackgroundGarcía-Ruiz, E., Reynés, B., Díaz‐Rúa, R., Ceresi, E., Oliver, P., & Palou, A. (2015) · International Journal of Obesity · doi:10.1038/ijo.2015.112 · Cited by 92
Decreased irisin secretion contributes to muscle insulin resistance in high-fat diet mice.
Yang, Z., Xu, C., Chen, Y., & Zhao, Q. (2015) · Europe PMC (PubMed Central) · Cited by 86
The Role of Exercise, Diet, and Cytokines in Preventing Obesity and Improving Adipose Tissue
ATAKAN, M. M., Koşar, Ş. N., Güzel, Y., Tin, H. T., & Yan, X. (2021) · Nutrients · doi:10.3390/nu13051459 · Cited by 96
“WAT-derived FNDC5/irisin represents ~28% of total circulating levels of the protein, with the remaining 72% likely derived from skeletal muscle [307,313,314], indicating that adipose tissue is not an essential source of irisin.”
BackgroundMoreno, M., Moreno‐Navarrete, J. M., Serrano, M., Ortega, F. J., Delgado, E., Sánchez-Ragnarsson, C., Valdés, S., Botas, P., Ricart, W., & Fernández‐Real, J. M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0124100 · Cited by 90
“Irisin has been proposed to be produced by adipocytes [11, 12], although in lower quantities.”
BackgroundIrisin, an exercise-induced bioactive peptide beneficial for health promotion during aging process
Zhang, H., Wu, X., Liang, J., Kirberger, M., & Chen, N. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101680 · Cited by 88
Albrecht, E., Schering, L., Buck, F., Vlach, K., Schober, H., Drevon, C. A., & Maak, S. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.01.016 · Cited by 93
“Many studies detected FNDC5 in a molecular weight range from 22 to 30 kDa in untreated muscle of different species [25,26,34,37,38].”
BackgroundResultIrisin, a Link among Fatty Liver Disease, Physical Inactivity and Insulin Resistance
Arias, M., Ranchal, I., Romero‐Gómez, M., & Crespo, J. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms151223163 · Cited by 87
“Recently, the production and release of irisin by adipose tissue has been demonstrated, which may be an indication that irisin is an adipo-myokine and not just a myokine (Figure 2) [80].”
BackgroundRocha‐Rodrigues, S., Rodrı́guez, A., Gouveia, A., Gonçalves, I. O., Becerril, S., Ramírez, B., Beleza, J., Frühbeck, G., Ascensão, A. A. M. R., & Magalhães, J. (2016) · Life Sciences · doi:10.1016/j.lfs.2016.09.023 · Cited by 88
Implication of Circulating Irisin Levels with Brown Adipose Tissue and Sarcopenia in Humans
Choi, H. Y., Kim, S., Park, J. W., Lee, N. S., Hwang, S. Y., Huh, J. Y., Hong, H. C., Yoo, H. J., Baik, S. H., Youn, B., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1195 · Cited by 86
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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