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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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Items 201–300 of 611
Association of circulating irisin levels with normal weight obesity, glycemic and lipid profile
Mehrabian, S., Taheri, E., Karkhaneh, M., Qorbani, M., & Hosseini, S. (2015) · Journal of Diabetes & Metabolic Disorders · doi:10.1186/s40200-016-0239-5 · Cited by 41
Reproductive effects of irisin: Initial in vitro studies
Poretsky, L., Islam, J., Avtanski, D. B., Lin, Y. K., Shen, Y., Hirth, Y., LESSER, M. L., Rosenwaks, Z., & Seto‐Young, D. (2017) · Reproductive Biology · doi:10.1016/j.repbio.2017.05.011 · Cited by 41
Irisin levels in the progression of diabetes in sedentary women
Duran, İ. D., Gülçelik, N. E., Ünal, M., Topçuoğlu, C., Sezer, S., Tuna, M. M., Berker, D. S., & Güler, S. (2015) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2015.07.098 · Cited by 41
“Some authors suggested the contribution of adipose tissue to circulating levels of irisin, and the expression of FNDC5 and secretion of irisin was demonstrated by an animal study [29,30].”
BackgroundIrisin enhances longevity by boosting SIRT1, AMPK, autophagy and telomerase
Sánchez, B., Muñoz-Pinto, M. F., & Cano, M. (2023) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2022.41 · Cited by 38
“10).”
Associations of betatrophin levels with irisin in Chinese women with normal glucose tolerance
Xie, X., Gao, T., Yang, M., Chen, P., Jin, H., Yang, L., & Yu, X. (2015) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-015-0019-2 · Cited by 40
“Betatrophin is a cytokine expressed in the liver and adipose tissue that increases islet β cell proliferation in insulin resistance [5,7,8], whereas irisin, which promotes white adipose tissue (WAT) “browning” and improves glucose tolerance in mice, is a myokine as well as an adipokine [17,26].”
BackgroundGmiat, A., Micielska, K., Kozłowska, M., Flis, D. J., Smaruj, M., Kujach, S., Jaworska, J., Lipińska, P., & Ziemann, E. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.07.004 · Cited by 44
Kazeminasab, F., Marandi, S. M., Ghaedi, K., Safaeinejad, Z., Esfarjani, F., & Nasr‐Esfahani, M. H. (2018) · Applied Physiology Nutrition and Metabolism · doi:10.1139/apnm-2017-0614 · Cited by 40
Siteneski, A., Olescowicz, G., Pazini, F. L., Camargo, A., Fraga, D. B., Brocardo, P. S., Gil‐Mohapel, J., Cunha, M. P., & Rodrigues, A. L. S. (2020) · Journal of Neural Transmission · doi:10.1007/s00702-020-02143-9 · Cited by 41
Irisin induces trophoblast differentiation via AMPK activation in the human placenta
Drewlo, S., Johnson, E., Kilburn, B. A., Kadam, L., Armistead, B., & Kohan‐Ghadr, H. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29613 · Cited by 40
Irisin, Exercise, and COVID-19
Alves, H. R., Lomba, G. S. B., Gonçalves-de-Albuquerque, C. F., & Burth, P. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.879066 · Cited by 41
“Based on the functional characterization of irisin, it may be defined as a myokine (1) and an adipokine released during exercise (2).”
BackgroundAdipokines in atherosclerosis: unraveling complex roles
Luo, J., He, Z., Li, Q., Lv, M., Cai, Y., Ke, W., Niu, X., & Zhang, Z. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1235953 · Cited by 44
Dihydromyricetin stimulates irisin secretion partially via the PGC-1α pathway
Zhou, Q., Chen, K., Liu, P., Gao, Y., Zou, D., Deng, H., Huang, Y., Zhang, Q., Zhu, J., & Mi, M. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.05.036 · Cited by 39
Tang, M., Chen, H., Wang, Y.-F., Ren, P., Chen, L., Xiao, T., Wang, B.-B., Pan, Y.-F., Tsang, B. K., Zabel, B. A., et al. (2016) · Scientific Reports · doi:10.1038/srep21328 · Cited by 39
The brown-fat-secreted adipokine neuregulin 4 is decreased in gestational diabetes mellitus
Kralisch, S., Hoffmann, A., Kratzsch, J., Blüher, M., Stümvoll, M., Faßhauer, M., & Ebert, T. (2017) · Diabetes & Metabolism · doi:10.1016/j.diabet.2017.06.001 · Cited by 38
“Interestingly, both prepartum neuregulin 4 and its relative changes are positively correlated with irisin, another metabolically beneficial [26] adipokine/myokine influencing BAT function [27,28].”
BackgroundBonfante, I. L. P., Chacon‐Mikahil, M. P. T., Brunelli, D. T., Gáspari, A. F., Duft, R. G., Oliveira, A. G., Araújo, T. G., Saad, M. J. A., & Cavaglieri, C. R. (2017) · Archives of Endocrinology and Metabolism · doi:10.1590/2359-3997000000305 · Cited by 39
“The body weight, free fat mass and triglycerides have been related to FNDC/ irisin (5,30,37), indicating that body composition, especially body fat, and serum lipids could has influence about levels of this peptides, however, it is important to mention that these correlations presented a fragile “r” values.”
BackgroundResultYamakage, H., Tanaka, M., Inoue, T., Odori, S., Kusakabe, T., & Satoh‐Asahara, N. (2019) · Journal of Diabetes Investigation · doi:10.1111/jdi.13179 · Cited by 39
Irisin levels in genetic and essential obesity: clues for a potential dual role
Mai, S., Grugni, G., Mele, C., Vietti, R., Vigna, L., Sartório, A., Aimaretti, G., Scacchi, M., & Marzullo, P. (2020) · Scientific Reports · doi:10.1038/s41598-020-57855-5 · Cited by 39
Effect of Long-Term Moderate Physical Exercise on Irisin between Normal Weight and Obese Men
Rashid, F. A., Abbas, H. J., Naser, N. A., & Ali, H. A. (2020) · The Scientific World JOURNAL · doi:10.1155/2020/1897027 · Cited by 39
“muscle and adipose tissue or by a positive feedback mechanism from adiposity and through itself by an autocrine effect [22, 23].”
BackgroundThe role of irisin in metabolic flexibility: Beyond adipose tissue browning
Shen, S., Liao, Q., Chen, X., Peng, C. Y., & Lin, L. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.03.019 · Cited by 42
Serum irisin and its regulation by hyperinsulinemia in women with polycystic ovary syndrome
Adamska, A., Karczewska‐Kupczewska, M., Łebkowska, A., Milewski, R. J., Górska, M., Otziomek, E., Nikołajuk, A., Wołczyński, S., & Kowalska, I. (2016) · Endocrine Journal · doi:10.1507/endocrj.ej16-0249 · Cited by 38
Irisin at the crossroads of inter-organ communications: Challenge and implications
Zhao, R. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.989135 · Cited by 40
“White adipose tissue (WAT) constitutes an alternative source of irisin contributing approximately one third total levels of circulating irisin, and the secretion of irisin in white adipose tissue significantly increases in response to exercise training (47).”
BackgroundElizondo‐Montemayor, L., Silva‐Platas, C., Torres‐Quintanilla, A., López, C. E. R., Ruiz‐Esparza, G. U., Reyes-Mendoza, E., & García‐Rivas, G. (2017) · BioMed Research International · doi:10.1155/2017/2628968 · Cited by 36
“For example, some studies in adult humans and animals have reported an increase in FNDC5/irisin secretion by adipose tissue after short-term endurance exercise [13].”
InfluentialIrisin Has a Protective Role against Osteoporosis in Ovariectomized Rats
Morgan, E. N., Alsharidah, A. S., Mousa, A., & Edrees, H. M. (2021) · BioMed Research International · doi:10.1155/2021/5570229 · Cited by 37
“Irisin is a peptide myokine released as a result of exercise [18, 19].”
BackgroundMechanism of CNS regulation by irisin, a multifunctional protein
Qi, J., Yang, L.-K., Wang, X., Wang, M., Li, X., Feng, B., Wu, Y., Liu, S., & Zhang, K. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.07.007 · Cited by 37
Khidr, E. G., Ali, S. S., Elshafey, M. M., & Fawzy, O. (2017) · Gene · doi:10.1016/j.gene.2017.05.010 · Cited by 35
“Irisin was reported to be released also from adipocytes (Roca-Rivada et al., 2013).”
BackgroundTekin, S., Beytur, A., Erden, Y., Beytur, A., Çiğremiş, Y., Vardı, N., Türköz, Y., Tekedereli, İ., & Sandal, S. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27541 · Cited by 35
“In addition, it has been indicated that irisin is synthesized in white adipose tissue, liver, skin, and nerve fibers (Aydin et al., 2013; Roca‐Rivada et al., 2013).”
BackgroundEffects of the FNDC5/Irisin on Elderly Dementia and Cognitive Impairment
Peng, J., & Wu, J. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.863901 · Cited by 42
“, 2017), reducing gluconeogenesis and promoting glycogen synthesis (Polyzos et al., 2013; Roca-Rivada et al., 2013).”
BackgroundAssociation of metabolic parameters and rs726344 in FNDC5 with serum irisin concentrations
Ebert, T., Kralisch, S., Wurst, U., Scholz, M. R., Stümvoll, M., Kovacs, P. L., Faßhauer, M., & Tönjes, A. (2015) · International Journal of Obesity · doi:10.1038/ijo.2015.157 · Cited by 35
Bargut, T. C. L., Martins, F. F., Santos, L. P., Aguila, M. B., & Mandarim-de-Lacerda, C. A. (2019) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2018.12.003 · Cited by 34
Immunohistochemical localization of irisin in mole rats(Spalax leucodon)
Gür, F. M., Timurkaan, S., Yalçın, M., GİRGİN, A., & Tarakçı, B. G. (2017) · Biotechnic & Histochemistry · doi:10.1080/10520295.2017.1303194 · Cited by 35
“…of irisin in various tissues of rat and mouse (Boström et al. 2012, Dun et al. 2013, Kuloglu et al. 2014, Aydin et al. 2014a,c, 2015, Roca-Rivada et al. 2013), human (MorenoNavarrete et al. 2013, Roca-Rivada et al. 2013, Aydin et al. 2014b,c) and crested porcupine (Gençer Tarakçı et al. 2016).”
BackgroundInfluentialIncreased FNDC5 is associated with insulin resistance in high fat‐fed mice
Guilford, B. L., Parson, J. C., Grote, C., Vick, S. N., Ryals, J. M., & Wright, D. (2017) · Physiological Reports · doi:10.14814/phy2.13319 · Cited by 35
“Subcutaneous adipose secreted and contained higher amounts of FNDC5 highlighting a “beneficial, protective” role of subcutaneous adipose, opposed to visceral adipose which is often associated with obesity and metabolic dysfunction (Roca-Rivada et al. 2013).”
BackgroundInfluentialBatitucci, G., Brandão, C., de Carvalho, F. G., Marchini, J. S., Pfrimer, K., Ferriolli, E., Cunha, F. Q., Papoti, M., Terrazas, S. I. B. M., Junqueira‐Franco, M. V. M., et al. (2019) · Cytokine · doi:10.1016/j.cyto.2019.154741 · Cited by 36
González-Gil, A. M., Peschard-Franco, M., Castillo, E. C., Gutierrez-DelBosque, G., Treviño, V., Silva‐Platas, C., Pérez-Villarreal, L. F., García‐Rivas, G., & Elizondo‐Montemayor, L. (2019) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-019-0458-2 · Cited by 34
“Although irisin was first identified as a myokine secreted by muscle in response to exercise, it was later identified to be also secreted by white adipose tissue [29], hence the term adipomyokine.”
BackgroundIrisin deletion induces a decrease in growth and fertility in mice
Luo, Y., Qiao, X., Ma, Y., Deng, H., Xu, C. C., & Xu, L. (2021) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-021-00702-7 · Cited by 34
Altay, D. U., Keha, E. E., Yaman, S. Ö., İnce, İ., Alver, A., Erdoğan, B., Canpolat, S., Çobanoğlu, Ü., & Menteşe, A. (2016) · QJM · doi:10.1093/qjmed/hcw074 · Cited by 34
Safarimosavi, S., Mohebbi, H., & Rohani, H. (2018) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000002709 · Cited by 35
“Irisin is not only a myokine liberated by muscle tissue, but also an adipokine released by adipose tissue, and given the fact that chronic exercise training is in close relationship with body fat reduction and body mass, a decrease in irisin level as a result of chronic exercise training could be expected (30,33).”
BackgroundWięcek, M., Szymura, J., Sproull, J., & Szyguła, Z. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9092797 · Cited by 33
“Irisin is a 29-amino acid fragment of the extracellular domain of the FNDC5 protein, the gene of which is expressed mainly in myocytes [36] and adipocytes [37].”
BackgroundThe emerging neuroprotective roles of exerkines in Alzheimer’s disease
Rody, T., Amorim, J. A. D., & Felice, F. G. D. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.965190 · Cited by 37
“Many studies detected the molecular weight range from 22 to 30 kDa of the FNDC5 in different species (Roca-Rivada et al., 2013; Brenmoeh et al., 2014; Löffler et al., 2015; Zügel et al., 2016).”
BackgroundPan, J.-A., Zhang, H., Yu, Q., Zhang, J.-F., Wang, C.-Q., Gu, J., & Chen, K. (2021) · The American Journal of the Medical Sciences · doi:10.1016/j.amjms.2021.02.020 · Cited by 34
Jia, Z., Wang, Z., Pan, H., Zhang, J., Wang, Q., Zhou, C., & Liu, J. (2024) · European journal of medical research · doi:10.1186/s40001-024-02176-w · Cited by 35
“In addition, irisin is also considered an adipokine [51, 52].”
Of mice and men: novel insights regarding constitutive and recruitable brown adipocytes
Townsend, K. L., & Tseng, Y.-H. (2015) · International Journal of Obesity Supplements · doi:10.1038/ijosup.2015.5 · Cited by 32
Factors Associated with White Fat Browning: New Regulators of Lipid Metabolism
Zhang, P., He, Y., Wu, S., Li, X., Lin, X., Gan, M., Chen, L., Zhao, Y., Niu, L., Zhang, S., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23147641 · Cited by 36
“However, the exercise-induced browning phenotype decreased significantly in the high-fat diet (HFD)-fed mice [71,72].”
BackgroundPGC-1 mediates the regulation of metformin in muscle irisin expression and function.
Yang, Z., Xu, C., Chen, Y., & Zhao, Q. (2015) · Europe PMC (PubMed Central) · Cited by 32
Long-term study of the association of adipokines and glucose variability with diabetic complications
Cha, J. J., Min, H. S., Kim, K., Lee, M. J., Lee, M., Kim, J. E., Song, H. K., Cha, D. R., & Kang, Y. S. (2016) · The Korean Journal of Internal Medicine · doi:10.3904/kjim.2016.114 · Cited by 32
“Recent studies have shown that irisin is also secreted from white adipose tissue and thus has the potential to protect against obesity and insulin resistance [31].”
BackgroundIrisinemia: A Novel Concept to Coin in Clinical Medicine?
Sanchis‐Gomar, F., & Pérez-Quilis, C. (2013) · Annals of Nutrition and Metabolism · doi:10.1159/000354090 · Cited by 31
Elbelt, U., Hofmann, T., & Stengel, A. (2013) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e328363bc65 · Cited by 30
Hu, J., Ke, Y., Wu, F., Liu, S., Ji, C., Zhu, X., & Zhang, Y. (2020) · Gastroenterology Research and Practice · doi:10.1155/2020/8818191 · Cited by 31
“The adipose tissue functions to synthesize and secrete irisin, and some scholars have believed that irisin is not only a myokine but also an adipocytokine [24 – 26].”
Exercise hormone irisin prevents physical inactivity-induced cognitive decline in mice
Park, J.-H., Kim, J., & Mikami, T. (2022) · Behavioural Brain Research · doi:10.1016/j.bbr.2022.114008 · Cited by 35
“Although circulating irisin is recognized as a myokine released from skeletal muscle, other organs besides skeletal muscle, such as fatty tissue, the kidneys, and liver, also reportedly release irisin [32,40].”
Irisin and Energy Metabolism and the Role of Irisin on Metabolic Syndrome
Aladag, T., Moğulkoç, R., & Baltacı, A. K. (2023) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557523666230411105506 · Cited by 30
Irisin/BDNF signaling in the muscle-brain axis and circadian system: A review
Inyushkin, A. N., Полетаев, В., Михайловна, И. Е., Сергеевич, К. И., & Inyushkin, A. A. (2023) · Journal of Biomedical Research · doi:10.7555/jbr.37.20230133 · Cited by 31
Circulating levels of irisin is elevated in hypothyroidism, a case-control study
Ateş, İ., Altay, M., Topçuoğlu, C., & Yılmaz, F. M. (2016) · Archives of Endocrinology and Metabolism · doi:10.1590/2359-3997000000077 · Cited by 30
Plasma Irisin Levels in Subjects with Type 1 Diabetes: Comparison with Healthy Controls
Tentolouris, A., Eleftheriadou, I., Tsilingiris, D., Anastasiou, I. A., Kosta, O. A., Mourouzis, I. S., Kokkinos, A. D., Pantos, C. I., Katsilambros, N. L., & Tentolouris, N. (2018) · Hormone and Metabolic Research · doi:10.1055/a-0748-6170 · Cited by 31
“It is known that in humans irisin is produced mainly in skeletal muscle, while subcutaneous fat is a secondary and less important source of irisin production [1, 3].”
BackgroundZhang, X., Hu, C., Wu, H., Ma, Z., & Tang, Q. (2020) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-00557-5 · Cited by 30
“FNDC5 is widely distributed in different human tissues, especially adipose tissue, and helps to maintain normal lipid metabolism [5, 187].”
BackgroundMakiel, K., Suder, A., Targosz, A., Maciejczyk, M., & Haim, A. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12010369 · Cited by 33
“In mice, IR originating from muscle accounts for ~72% of the total level of the hormone in circulation, and the remaining 28% probably originates in adipose tissue [10].”
BackgroundLi, X., Fang, W., Hu, Y., Wang, Y., & Li, J. (2015) · Gene · doi:10.1016/j.gene.2015.06.022 · Cited by 31
Impact of adipokines and myokines on fat browning
Rodríguez, A., Catalán, V., Ramírez, B., Unamuno, X., Portincasa, P., Gómez‐Ambrosi, J., Frühbeck, G., & Becerril, S. (2020) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-020-00736-2 · Cited by 31
“Irisin is not only secreted by skeletal muscle but also, to a lesser extent, by AT, with an important autocrine and endocrine function [93, 113].”
BackgroundFrom Exercise to Cognitive Performance: Role of Irisin
Pesce, M., Fratta, I. L., Paolucci, T., Grilli, A., Patruno, A., Agostini, F., Bernetti, A., Mangone, M., Paoloni, M., Invernizzi, M., et al. (2021) · Applied Sciences · doi:10.3390/app11157120 · Cited by 29
Torabi, A., Reisi, J., Kargarfard, M., & Mansourian, M. (2024) · International Journal of Preventive Medicine · doi:10.4103/ijpvm.ijpvm_76_23 · Cited by 28
“[5] Analyzing the individual effects of each type of exercise protocol in each group, it was found that in the overweight group, resistance training, HIIT, and aerobics had a significant effect size, while combined exercises showed a non‑significant effect size.”
BackgroundSerum levels of the adipomyokine irisin in patients with chronic kidney disease
Rodríguez–Carmona, A., Fontán, M. P., Sangiao‐Alvarellos, S., Falcón, T. G., Bello, M. L. P., Muñíz, A. L., & Cordido, F. (2016) · Nefrología (English Edition) · doi:10.1016/j.nefroe.2016.11.011 · Cited by 28
Bashar, S. M., Samir, S. M., & Boraie, M. Z. (2018) · Journal of Basic and Clinical Physiology and Pharmacology · doi:10.1515/jbcpp-2018-0090 · Cited by 28
Karampatsou, S., Genitsaridi, S. M., Michos, A. G., Kourkouni, Ε., Kourlaba, G., Kassari, P., Μanios, Y., & Charmandari, E. (2021) · Nutrients · doi:10.3390/nu13041274 · Cited by 28
Rahimi, G. R. M., Hejazi, K., & Hofmeister, M. (2022) · EXCLI journal · doi:10.17179/excli2022-4703 · Cited by 36
“…FNDC5, irisin is recognized as the target gene for PGC1-α. mRNA FNDC5 is expressed higher in muscles than in other organs (Huh et al., 2012), and the increased expression of FNDC5 in skeletal muscles is significantly linked to the serum level of irisin (Huh et al., 2012; Roca-Rivada et al., 2013).”
BackgroundDifferent adipose tissue depots: Metabolic implications and effects of surgical removal
Marcadenti, A., & de Abreu-Silva, E. O. (2015) · Endocrinología y Nutrición · doi:10.1016/j.endonu.2015.05.010 · Cited by 28
“Irisin activates thermogenesis in adipose tissue, stimulates beige adipose tissue and the ‘‘darkening’’ capacity of WAT in vivo and in vitro, promoting some metabolic functions and energy dissipation in thus cells through an increase in UCP1 expression.16,17 Recently, irisin was found to be secreted by adipocytes as w…”
BackgroundInfluentialZależne od czasu zmiany stężenia irisiny u pacjentów z jawną niedoczynnością tarczycy
Zybek‐Kocik, A., Sawicka‐Gutaj, N., Wrotkowska, E., Sowiński, J., & Ruchała, M. (2016) · Endokrynologia Polska · doi:10.5603/ep.a2016.0030 · Cited by 28
Irisin interaction with adipose tissue secretions by exercise training and flaxseed oil supplement
Shirvani, H., & Rahmati-Ahmadabad, S. (2019) · Lipids in Health and Disease · doi:10.1186/s12944-019-0960-4 · Cited by 27
Kerstholt, N., Ewert, R., Nauck, M., Spielhagen, T., Bollmann, T., Stubbe, B., Felix, S. B., Wallaschofski, H., Gläser, S., & Friedrich, N. (2015) · BMC Pulmonary Medicine · doi:10.1186/s12890-015-0035-x · Cited by 26
“Currently irisin has been found to be an adipokine which is secreted by white adipose tissue and especially by subcutaneous adipose tissue [30].”
BackgroundNiranjan, S. B., Belwalkar, S. V., Tambe, S. M., Venkataraman, K., & Mookhtiar, K. A. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.08.112 · Cited by 26
Komosińska‐Vassev, K., Gala, O. M., Olczyk, K., Jura-Półtorak, A., & Olczyk, P. (2020) · Biomolecules · doi:10.3390/biom10091304 · Cited by 26
“hypothesized that pathological conditions, like obesity, make adipose tissue more relevant for FNDC5/ irisin secretion than other body tissues [51].”
BackgroundWaseem, R., Shamsi, A., Shahbaz, M., Khan, T., Kazim, S. N., Ahmad, F., Hassan, M. I., & Islam, A. (2021) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2021.132141 · Cited by 26
Impact of a cafeteria diet and daily physical training on the rat serum metabolome
Suárez‐Garcia, S., Bas-Prior, J. M. D., Caimari, A., Escorihuela, R. M., Arola, L., & Suárez, M. (2017) · PLoS ONE · doi:10.1371/journal.pone.0171970 · Cited by 26
The association between irisin and muscle metabolism in different thyroid disorders
Zybek‐Kocik, A., Sawicka‐Gutaj, N., Szczepanek‐Parulska, E., Andrusiewicz, M., Waligórska‐Stachura, J., Białas, P., Krauze, T., Guzik, P., Skrobisz, J., & Ruchała, M. (2017) · Clinical Endocrinology · doi:10.1111/cen.13527 · Cited by 26
Li, H., Zhang, C., Liu, J., Xie, W., Xu, W., Liang, F., Huang, K., & He, X. (2019) · PLoS ONE · doi:10.1371/journal.pone.0220310 · Cited by 26
Irisin Protects Musculoskeletal Homeostasis via a Mitochondrial Quality Control Mechanism
Zhao, C., Wu, Y., Zhu, S., Liu, H., & Xu, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251810116 · Cited by 30
“Beyond its role as a myokine, irisin is also expressed and secreted in adipose tissue, particularly in subcutaneous and visceral adipose tissues [65].”
BackgroundAbdi, A., Mehrabani, J., Nordvall, M., Wong, A., Fallah, A., & Bagheri, R. (2020) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2020.1716018 · Cited by 26
“For instance, a decrease in UCP1 mRNA expression in BAT has been documented in rats following 3weeks of endurance training (Roca-Rivada et al. 2013).”
BackgroundInfluentialInvolvement of the p62/Nrf2/HO-1 pathway in the browning effect of irisin in 3T3-L1 adipocytes
Tsai, Y.-C., Wang, C.-W., Wen, B.-Y., Hsieh, P., Lee, Y., Yen, M., & Cheng, P. (2020) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2020.110915 · Cited by 25
The Acute Effects of Swimming Exercise on PGC-1α-FNDC5/Irisin-UCP1 Expression in Male C57BL/6J Mice
Cho, E., Jeong, D. Y., Kim, J. G., & Lee, S. (2021) · Metabolites · doi:10.3390/metabo11020111 · Cited by 25
“shown that FNDC5 protein was produced and released from both visceral and subcutaneous adipose tissue in a rat model [23].”
BackgroundCrucial Regulatory Role of Organokines in Relation to Metabolic Changes in Non-Diabetic Obesity
Lőrincz, H., Somodi, S., Ratku, B., Harangi, M., & Paragh, G. (2023) · Metabolites · doi:10.3390/metabo13020270 · Cited by 26
Kim, S., Park, D., LEE, S.-H., Kwak, H., & Kang, J. (2023) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000003136 · Cited by 25
The Role of FNDC5/Irisin in Cardiovascular Disease
Grzeszczuk, M., Dzięgiel, P., & Nowińska, K. (2024) · Cells · doi:10.3390/cells13030277 · Cited by 26
“Research on Ir has indicated that it is commonly found in the human body—in the heart, brain, skeletal muscle, liver, kidney, lung, spleen, skin, secretory glands, adipose tissue and myelin sheaths of nerve fibers [1–5].”
BackgroundMatsakas, A., Prosdocimo, D. A., Mitchell, R., Collins‐Hooper, H., Giallourou, N., Swann, J. R., Potter, P. K., Epting, T., Jain, M. K., & Patel, K. (2015) · Skeletal Muscle · doi:10.1186/s13395-015-0063-5 · Cited by 28
“Recent studies have found that white fat expresses this protein and regulates its metabolic properties in an autocrine fashion [33].”
Exercise-Induced Circulating Irisin Level Is Correlated with Improved Cardiac Function in Rats
Seo, D. Y., Bae, J. H., Kim, T. N., Kwak, H., Kha, P. T., & Han, J. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17113863 · Cited by 26
“Irisin is released from the skeletal muscle [4] and adipose tissue [14,15] during exercise.”
BackgroundBubak, M. P., Heesch, M., Shute, R. J., Dinan, N. E., Laursen, T. L., Salle, D. T. L., & Slivka, D. R. (2017) · International journal of exercise science · doi:10.70252/xkmw8211 · Cited by 24
“BAT has non-shivering thermogenic capabilities due to an increase in mitochondrial density and thus has increased metabolic activity compared to WAT (2).”
BackgroundInfluentialA Bibliometric Analysis of the Literature on Irisin from 2012–2021
Liu, J., Qi, B., Gan, L., Shen, Y., & Zou, Y. F. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19106153 · Cited by 25
“firstly revealed that white adipose tissue (WAT) also secreted irisin, demonstrating that irisin is not just a myokine liberated by muscle tissue but an adipokine released by adipose tissue [19].”
BackgroundExercise and Metabolic Health: The Emerging Roles of Novel Exerkines
Yazgan, B., Türkel, İ., Özerkliğ, B., ATAKAN, M. M., Aktitiz, S., & Koşar, Ş. N. (2022) · Current Protein and Peptide Science · doi:10.2174/1389203723666220629163524 · Cited by 25
The Role of Irisin throughout Women’s Life Span
Barbagallo, F., Cannarella, R., Garofalo, V., Marino, M., Vignera, S. L., Condorelli, R. A., Tiranini, L., Nappi, R. E., & Calogero, A. E. (2023) · Biomedicines · doi:10.3390/biomedicines11123260 · Cited by 25
“Furthermore, the recent discovery that irisin is also secreted by WAT could partly explain the gender difference, since the distribution of WAT itself is gender dimorphic [23].”
BackgroundMechanisms by which obesity regulates inflammation and anti-tumor immunity in cancer
Miracle, C. E., McCallister, C. L., Egleton, R. D., & Salisbury, T. B. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.150437 · Cited by 24
Serum, Saliva, and Urine Irisin with and without Acute Appendicitis and Abdominal Pain
Bakal, Ü., Aydın, S., Saraç, M., Kuloğlu, T., Kalaycı, M. Z., Artaş, G., Yardım, M., & Kazez, A. (2016) · Biochemistry Insights · doi:10.4137/bci.s39671 · Cited by 24
Does iris(in) bring bad news or good news?
Buscemi, S., Corleo, D., Buscemi, C., & Giordano, C. S. D. S. (2017) · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity · doi:10.1007/s40519-017-0431-8 · Cited by 24
“Interestingly, it was recently reported that irisin is also an adipokine, its expression having been detected in both mouse [32] and human adipose tissue [33].”
BackgroundExercise in Diabetic Nephropathy: Protective Effects and Molecular Mechanism
Li, R.-Y., & Guo, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25073605 · Cited by 27
“Irisin Endurance training can induce the release of irisin from muscle or adipose tissue, possibly due to the activation of its upstream regulator peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1 α ) by exercise [119,120].”
BackgroundIrisin in idiopathic foetal growth restriction
Çağlar, M., Göksu, M., İsenlik, B. S., Yavuzcan, A., Yılmaz, M., Üstün, Y., Aydın, S., & Kumru, S. (2014) · Journal of Endocrinological Investigation · doi:10.1007/s40618-014-0078-5 · Cited by 23
“More recently, irisin has been reported to serve not only as a myokine, but also as an adipokine, because the FNDC5 protein is secreted by white adipose tissue [19].”
BackgroundIrisin Regulates the Functions of Hepatic Stellate Cells
Dong, H. N., Park, S. Y., Le, C. T., Choi, D.-H., & Cho, E.-H. (2020) · Endocrinology and Metabolism · doi:10.3803/enm.2020.658 · Cited by 24
“org Copyright © 2020 Korean Endocrine Society sources of irisin synthesis and secretion on a smaller scale [10].”
BackgroundJiang, S., Piao, L., Ma, E. B., Ha, H., & Huh, J. Y. (2021) · Biomolecules · doi:10.3390/biom11020322 · Cited by 25
“In 2013, two different groups first reported the evidence for irisin as an adipokine [17,30].”
BackgroundResultInfluentialŚliwicka, E., Cisoń, T., Straburzyńska‐Lupa, A., & Pilaczyńska-Szczȩśniak, Ł. (2020) · Scientific Reports · doi:10.1038/s41598-020-63002-x · Cited by 23
Relation of serum irisin levels to obesity and non-alcoholic fatty liver disease
Ulualan, G., Kiraz, Z. K., & Kırel, B. (2022) · The Turkish Journal of Pediatrics · doi:10.24953/turkjped.2020.3003 · Cited by 22
Adipokines regulate the development and progression of MASLD through organellar oxidative stress
Zhao, K., Zhang, H., Ding, W., Yu, X., Hou, Y., Liu, X., Li, X., & Wang, X. (2025) · Hepatology Communications · doi:10.1097/hc9.0000000000000639 · Cited by 25
Expression, purification and biological characterisation of recombinant human irisin (12.5 kDa)
Panati, K., Narala, V. R., Narasimha, V. R., Derangula, M., Tatireddigari, V. R. R. A., & Yeguvapalli, S. (2018) · Journal of Genetic Engineering and Biotechnology · doi:10.1016/j.jgeb.2018.06.007 · Cited by 23
“The size of rh-irisin was correlated with calculated size from deduced amino acid sequence and found to be consistent with previous reports [7].”
BackgroundResultThe myokine irisin: localization and effects in swine late medium and large antral ovarian follicle
Basini, G., Bussolati, S., Iannarelli, M., Ragionieri, L., Grolli, S., Ramoni, R., Dodi, A., Gazza, F., & Grasselli, F. (2020) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2020.106576 · Cited by 22
Irisin-Associated Neuroprotective and Rehabilitative Strategies for Stroke
Huberman, M. A., d’Adesky, N., Niazi, Q. B., Pérez‐Pinzón, M. A., Bramlett, H. M., & Raval, A. P. (2021) · NeuroMolecular Medicine · doi:10.1007/s12017-021-08666-y · Cited by 23
“Fiber type switching may be of significance because irisin is predominately secreted from oxidative muscle fibers (Bostrom et al., 2012; Roca-Rivada et al., 2013).”
BackgroundVita, F., Gangemi, S., Pioggia, G., Trimarchi, F., & Mauro, D. D. (2022) · Medicina · doi:10.3390/medicina58060767 · Cited by 20
“It was yet reported that WAT produced FNDC5/irisin after physical activity [64], and the marked transcription of typical BAT-like adipocytes gene, showed in myostatin KO mice, underlined the power to sustain an anabolic effect on the bones [65].”
BackgroundFélix‐Soriano, E., Sáinź, N., Gil‐Iturbe, E., Castilla‐Madrigal, R., Celay, J., Fernández‐Galilea, M., Pejenaute, Á., Lostao, M. P., Martinez-Climent, J. A., & Moreno-Aliaga, M. J. (2023) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-023-00964-2 · Cited by 23
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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