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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Irisin is not a protein exclusively secreted by muscle tissue.
“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
Both subcutaneous and visceral adipose tissue from rats secreted FNDC5/irisin under the stimulus of endurance training.
“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
White adipose tissue also secretes FNDC5, the precursor of irisin, indicating that irisin is not only a myokine but also an adipokine.
“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
FNDC-5 secretion is around 40% higher in slow-oxidative fibre-type muscle (soleus) than in fast-glycolytic fibre-type muscle (gastrocnemius).
“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].”
Irisin is mainly secreted by skeletal muscle cells, although some secretion was also reported in WAT and, to a lesser extent, in BAT.
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
Wenz, T., Rossi, S. G., Rotundo, R. L., Spiegelman, B. M., & Moraes, C. T. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911570106 · Cited by 600 · see citing works
RetractedA PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis
Boström, P., Wu, J., Jedrychowski, M. P., Korde, A., Ye, L., Lo, J. C., Rasbach, K. A., Boström, E. A., Choi, J. H., Long, J. Z., et al. (2012) · Nature · doi:10.1038/nature10777 · Cited by 4,810 · see citing works
Identification and Importance of Brown Adipose Tissue in Adult Humans
Cypess, A. M., Lehman, S., Williams, G., Tal, I., Rodman, D., Goldfine, A. B., Kuo, F. C., Palmer, E. L., Tseng, Y.-H., Doria, A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810780 · Cited by 4,399 · see citing works
A Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis
Puigserver, P., Wu, Z., Park, C. W., Graves, R., Wright, M., & Spiegelman, B. M. (1998) · Cell · doi:10.1016/s0092-8674(00)81410-5 · Cited by 3,864 · see citing works
Functional Brown Adipose Tissue in Healthy Adults
Virtanen, K. A., Lidell, M. E., Orava, J., Heglind, M., Westergren, R., Niemi, T., Taittonen, M., Laine, J., Savisto, N.-J., Enerbäck, S., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808949 · Cited by 3,058 · see citing works
Muscles, exercise and obesity: skeletal muscle as a secretory organ
Pedersen, B. K., & Febbraio, M. A. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.49 · Cited by 2,909 · see citing works
Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6
Pedersen, B. K., & Febbraio, M. A. (2008) · Physiological Reviews · doi:10.1152/physrev.90100.2007 · Cited by 2,388 · see citing works
Subcutaneous and visceral adipose tissue: Structural and functional differences
Ibrahim, M. M. (2010) · Obesity Reviews · doi:10.1111/j.1467-789x.2009.00623.x · Cited by 2,238 · see citing works
High Incidence of Metabolically Active Brown Adipose Tissue in Healthy Adult Humans
Saito, M., Okamatsu-Ogura, Y., Matsushita, M., Watanabe, K., Yoneshiro, T., Nio-Kobayashi, J., Iwanaga, T., Miyagawa, M., Kameya, T., Nakada, K., et al. (2009) · Diabetes · doi:10.2337/db09-0530 · Cited by 1,848 · see citing works
Unexpected evidence for active brown adipose tissue in adult humans
Nedergaard, J., Bengtsson, T., & Cannon, B. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00691.2006 · Cited by 1,824 · see citing works
An established pre-adipose cell line and its differentiation in culture
Green, H., & Meuth, M. (1974) · Cell · doi:10.1016/0092-8674(74)90116-0 · Cited by 1,108 · see citing works
Disordered lipid metabolism and the pathogenesis of insulin resistance.
Savage, D. B., Petersen, K. F., & Shulman, G. I. (2007) · Physiological Reviews · doi:10.1152/physrev.00024.2006 · Cited by 1,107 · see citing works
The role of exercise and PGC1α in inflammation and chronic disease
Handschin, C., & Spiegelman, B. M. (2008) · Nature · doi:10.1038/nature07206 · Cited by 1,083 · see citing works
Huh, J. Y., Panagiotou, G., Mougios, V., Brinkoetter, M., Vamvini, M. T., Schneider, B. E., & Mantzoros, C. S. (2012) · Metabolism · doi:10.1016/j.metabol.2012.09.002 · Cited by 1,040 · see citing works
Integrated Genomic and Proteomic Analyses of Gene Expression in Mammalian Cells
Tian, Q., Stepaniants, S., Mao, M., Weng, L., Feetham, M. C., Doyle, M. J., Yi, E. C., Dai, H. A., Thórsson, V., Eng, J. K., et al. (2004) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m400055-mcp200 · Cited by 778 · see citing works
Free fatty acids and insulin resistance
Delarue, J., & Magnan, C. (2007) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e328042ba90 · Cited by 463 · see citing works
Self-starvation of rats living in activity wheels on a restricted feeding schedule.
Routtenberg, A., & Kuznesof, A. W. (1967) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0025205 · Cited by 450 · see citing works
Stengel, A., Hofmann, T., Goebel-Stengel, M., Elbelt, U., Kobelt, P., & Klapp, B. (2013) · Peptides · doi:10.1016/j.peptides.2012.11.014 · Cited by 439 · see citing works
Brown Adipose Tissue, Whole‐Body Energy Expenditure, and Thermogenesis in Healthy Adult Men
Yoneshiro, T., Aita, S., Matsushita, M., Kameya, T., Nakada, K., Kawai, Y., & Saito, M. (2010) · Obesity · doi:10.1038/oby.2010.105 · Cited by 418 · see citing works
Is irisin a human exercise gene?
Timmons, J. A., Baar, K., Davidsen, P. K., & Atherton, P. J. (2012) · Nature · doi:10.1038/nature11364 · Cited by 388 · see citing works
Enerbäck, S. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.03.008 · Cited by 367 · see citing works
Review on leptin and adiponectin responses and adaptations to acute and chronic exercise
Bouassida, A., Chamari, K., Zaouali, M., Feki, Y., Zbidi, A., & Tabka, Z. (2010) · British Journal of Sports Medicine · doi:10.1136/bjsm.2008.046151 · Cited by 290 · see citing works
Characterization of the Human Visceral Adipose Tissue Secretome
Álvarez‐Llamas, G., Szalowska, E., de Vries, M. P., Weening, D., Landman, K., Hoek, A., Wolffenbuttel, B. H. R., Roelofsen, H., & Vonk, R. J. (2007) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m600265-mcp200 · Cited by 231 · see citing works
Approaches to the study of the cell secretome
Hathout, Y. (2007) · Expert Review of Proteomics · doi:10.1586/14789450.4.2.239 · Cited by 203 · see citing works
Integrating gene and protein expression data: pattern analysis and profile mining
Cox, B., Kislinger, T., & Emili, A. (2005) · Methods · doi:10.1016/j.ymeth.2004.08.021 · Cited by 176 · see citing works
Timmons, J. A., Larsson, O. S., Jansson, E., Fischer, H., Gustafsson, T. P., Greenhaff, P. L., Ridden, J., Rachman, J., Peyrard‐Janvid, M., Wahlestedt, C., et al. (2005) · The FASEB Journal · doi:10.1096/fj.04-1980com · Cited by 158 · see citing works
Castillo-Quan, J. I. (2012) · Disease Models & Mechanisms · doi:10.1242/dmm.009894 · Cited by 157 · see citing works
Proteomic identification of multitasking proteins in unexpected locations complicates drug targeting
Butler, G. S., & Overall, C. M. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2945 · Cited by 143 · see citing works
Kelly, D. P. (2012) · Science · doi:10.1126/science.1221688 · Cited by 132 · see citing works
The role of fat topology in the risk of disease
Matsuzawa, Y. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.243 · Cited by 125 · see citing works
Ruschke, K., Fishbein, L. M., Dietrich, A., Klöting, N., Tönjes, A., Oberbach, A., Faßhauer, M., Jenkner, J., Schön, M. R., Stümvoll, M., et al. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0767 · Cited by 116 · see citing works
Villarroya, F. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.02.010 · Cited by 104 · see citing works
Irisin: A new potential hormonal target for the treatment of obesity and type 2 diabetes
Sanchis‐Gomar, F., Lippi, G., Mayero, S., Pérez-Quilis, C., & García‐Giménez, J. L. (2012) · Journal of Diabetes · doi:10.1111/j.1753-0407.2012.00194.x · Cited by 96 · see citing works
Why are we shaped differently, and why does it matter?
Santosa, S., & Jensen, M. D. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90357.2008 · Cited by 87 · see citing works
Brown fat thermogenesis and body weight regulation in mice: relevance to humans
Kozak, L. P., Koza, R. A., & Anunciado‐Koza, R. P. (2010) · International Journal of Obesity · doi:10.1038/ijo.2010.179 · Cited by 78 · see citing works
Secretome analysis of rat adipose tissues shows location-specific roles for each depot type
Roca-Rivada, A., Alonso, J., Al–Massadi, O., Castelao, C., Peinado, J. R., Seoane, L. M., Casanueva, F. F., & Pardo, M. (2011) · Journal of Proteomics · doi:10.1016/j.jprot.2011.03.010 · Cited by 75 · see citing works
Characterization of the human visceral adipose tissue secretome
Álvarez‐Llamas, G., Szalowska, E., de Vries, M. P., Weening, D., Landman, K., Hoek, A., Wolffenbuttel, B. H. R., Roelofsen, H., & Vonk, R. J. (2007) · University of Groningen research database (University of Groningen / Centre for Information Technology) · Cited by 75 · see citing works
Pardo, M., García, Á. G., Antrobus, R., Blanco, M. J., Dwek, R. A., & Zitzmann, N. (2007) · Journal of Proteome Research · doi:10.1021/pr070021t · Cited by 58 · see citing works
Pardo, M., Roca-Rivada, A., Al–Massadi, O., Seoane, L. M., Camiña, J. P., & Casanueva, F. F. (2010) · Peptides · doi:10.1016/j.peptides.2010.06.022 · Cited by 48 · see citing works
Roca-Rivada, A., Al–Massadi, O., Castelao, C., Senín, L. L., Alonso, J., Seoane, L. M., García‐Caballero, T., Casanueva, F. F., & Pardo, M. (2012) · Journal of Proteomics · doi:10.1016/j.jprot.2012.06.037 · Cited by 48 · see citing works
Al–Massadi, O., Crujeiras, A. B., González, M. C. R., Pardo, M., Diéguez, C., Casanueva, F. F., & Seoane, L. M. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00057.2010 · Cited by 30 · see citing works
Irisin—behind the benefits of exercise
Cunha, A. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.11 · Cited by 23 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
Kalinkovich, A., & Livshits, G. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.008 · Cited by 882 · see citing works
Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans
Lee, P., Linderman, J. D., Smith, S., Brychta, R. J., Wang, J., Idelson, C., Perron, R. M., Werner, C. D., Phan, G. Q., Kammula, U. S., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.12.017 · Cited by 802 · see citing works
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 · see citing works
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 513 · see citing works
Circulating irisin in relation to insulin resistance and the metabolic syndrome.
Park, K., Zaichenko, L., Brinkoetter, M. T., Thakkar, B., Sahin-Efe, A., Joung, K., Tsoukas, M. A., Geladari, E., Huh, J., Dinçer, F., et al. (2013) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2013-2373 · Cited by 527 · see citing works
Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases
Demine, S., Renard, P., & Arnould, T. (2019) · Cells · doi:10.3390/cells8080795 · Cited by 476 · see citing works
Peirce, V. J., Carobbio, S., & Vidal‐Puig, A. (2014) · Nature · doi:10.1038/nature13477 · Cited by 414 · see citing works
Kurdiova, T., Balaz, M., Vician, M., Maderova, D., Vlcek, M., Valkovic, L., Srbecky, M., Imrich, R., Kyselovicova, O., Belan, V., et al. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2013.264655 · Cited by 401 · see citing works
Leal, L. G., Lopes, M. A., & Batista, M. L. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01307 · Cited by 382 · see citing works
Irisin – a myth rather than an exercise-inducible myokine
Albrecht, E., Norheim, F., Thiede, B., Holen, T., Ohashi, T., Schering, L., Lee-Ødegård, S., Brenmoehl, J., Thomas, S., Drevon, C. A., et al. (2015) · Scientific Reports · doi:10.1038/srep08889 · Cited by 346 · see citing works
Reza, M. M., Subramaniyam, N., Sim, C. M., Ge, X., Sathiakumar, D., McFarlane, C., Sharma, M., & Kambadur, R. (2017) · Nature Communications · doi:10.1038/s41467-017-01131-0 · Cited by 335 · see citing works
Huh, J. Y., Dincer, F., Mesfum, E., & Mantzoros, C. S. (2014) · International Journal of Obesity · doi:10.1038/ijo.2014.42 · Cited by 309 · see citing works
Li, D., Li, Y., Yuan, H., Qu, L., & Wang, P. (2016) · Metabolism · doi:10.1016/j.metabol.2016.12.003 · Cited by 308 · see citing works
Irisin: A Hope in Understanding and Managing Obesity and Metabolic Syndrome
Arhire, L. I., Mihalache, L., & Covașă, M. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00524 · Cited by 306 · see citing works
Adipo-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 · see citing works
Pekkala, 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 · see citing works
Rodrı́guez, 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 281 · see citing works
Cytokines and abnormal glucose and lipid metabolism
Shi, J., Fan, J., Su, Q., & Yang, Z. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00703 · Cited by 282 · see citing works
Polyzos, S. A., Anastasilakis, A. D., Efstathiadou, Z. A., Makras, P., Perakakis, N., Kountouras, J., & Mantzoros, C. S. (2018) · Endocrine · doi:10.1007/s12020-017-1476-1 · Cited by 262 · see citing works
Three new players in energy regulation: Preptin, adropin and irisin
Aydın, S. (2014) · Peptides · doi:10.1016/j.peptides.2014.03.021 · Cited by 258 · see citing works
Ren, Y., Zhao, H., Yin, C., Lan, X., Wu, L., Du, X., Griffiths, H. R., & Gao, D. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.873699 · Cited by 260 · see citing works
Progress and Challenges in the Biology of FNDC5 and Irisin
Maak, S., Norheim, F., Drevon, C. A., & Erickson, H. P. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnab003 · Cited by 247 · see citing works
Xiong, X.-Q., Chen, D., Sun, H.-J., Ding, L., Wang, J.-J., Chen, Q., Li, Y.-H., Zhou, Y.-B., Han, Y., Zhang, F., et al. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.06.017 · Cited by 242 · see citing works
The role of exercise-induced myokines in regulating metabolism
Huh, J. Y. (2018) · Archives of Pharmacal Research · doi:10.1007/s12272-017-0994-y · Cited by 242 · see citing works
The 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 240 · see citing works
Aydin, S., Kuloglu, T., Aydin, S., Kalayci, M., Yilmaz, M., Cakmak, T., Albayrak, S., Gungor, S., Colakoglu, N., & Ozercan, İ. H. (2014) · Peptides · doi:10.1016/j.peptides.2014.09.014 · Cited by 233 · see citing works
Biomarkers in sarcopenia: A multifactorial approach
Curcio, F., Ferro, G., Basile, C., Liguori, I., Parrella, P., Pirozzi, F., Della‐Morte, D., Gargiulo, G., Testa, G., Tocchetti, C. G., et al. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.09.007 · Cited by 225 · see citing works
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 216 · see citing works
Serum 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 213 · see citing works
Irisin and FNDC5 in retrospect
Erickson, H. (2013) · Adipocyte · doi:10.4161/adip.26082 · Cited by 211 · see citing works
Metabolic adaptation in obesity and type ii diabetes: myokines, adipokines and hepatokines
Oh, K.-J., Lee, D., Kim, W., Han, B., Lee, S., & Bae, K.-H. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms18010008 · Cited by 210 · see citing works
Resistance exercise induces a greater irisin response than endurance exercise
Tsuchiya, Y., Ando, D., Takamatsu, K., & Goto, K. (2015) · Metabolism · doi:10.1016/j.metabol.2015.05.010 · Cited by 207 · see citing works
Mazur-Bialy, A. I., Pocheć, E., & Zarawski, M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040701 · Cited by 203 · see citing works
Browning 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 204 · see citing works
Irisin exerts dual effects on browning and adipogenesis of human white adipocytes.
Zhang, Y., Xie, C., Wang, H., Foss, R. M., Clare, M., George, E., Li, S.-W., Katz, A. J., Cheng, H., Ding, Y.-S., et al. (2016) · American Journal of Physiology. Endocrinology and Metabolism · doi:10.1152/ajpendo.00094.2016 · Cited by 187 · see citing works
Crosstalk between adipokines and myokines in fat browning
Rodrı́guez, A., Becerril, S., Ezquerro, S., Méndez-Giménez, L., & Frühbeck, G. (2016) · Acta Physiologica · doi:10.1111/apha.12686 · Cited by 192 · see citing works
Sarcopenia – The search for emerging biomarkers
Kalinkovich, A., & Livshits, G. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.05.001 · Cited by 187 · see citing works
Anastasilakis, A. D., Pοlyzos, S. A., Saridakis, Z. G., Kynigopoulos, G., Skouvaklidou, E. C., Molyvas, D., Vasiloglou, M. F., Apostolou, A., Karagiozoglou‐Lampoudi, Τ., Siopi, A., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1367 · Cited by 186 · see citing works
Wu, M. V., Bikopoulos, G. J., Hung, S., & Ceddia, R. B. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.591008 · Cited by 184 · see citing works
Inter‐organ communication: a gatekeeper for metabolic health
Castillo‐Armengol, J., Fajas, L., & Lopez‐Mejia, I. C. (2019) · The EMBO Reports · doi:10.15252/embr.201947903 · Cited by 178 · see citing works
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 178 · see citing works
Tsuchiya, Y., Ando, D., Goto, K., Kiuchi, M., Yamakita, M., & Koyama, K. (2014) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.233.135 · Cited by 176 · see citing works
Zhang, J., Valverde, P., Zhu, X., Murray, D., Wu, Y., Yu, L., Jiang, H., Dard, M. M., Huang, J., Zhi-wei, X., et al. (2017) · Bone Research · doi:10.1038/boneres.2016.56 · Cited by 175 · see citing works
Chang, J. S., Kim, T. H., Nguyen, T. T., Park, K., Kim, N., & Kong, I. D. (2017) · Geriatrics & Gerontology International · doi:10.1111/ggi.13030 · Cited by 166 · see citing works
Piya, M. K., Harte, A. L., Sivakumar, K., Tripathi, G., Voyias, P. D., James, S. G., Sabico, S., Al‐Daghri, N. M., Saravanan, P., Barber, T. M., et al. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00308.2013 · Cited by 167 · see citing works
Irisin 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 163 · see citing works
Adipose Organ Development and Remodeling
Cinti, S. (2018) · Comprehensive physiology · doi:10.1002/cphy.c170042 · Cited by 187 · see citing works
Irisin, an exercise‐induced myokine as a metabolic regulator: an updated narrative review
Chen, N., Li, Q., Liu, J., & Jia, S. (2015) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2660 · Cited by 164 · see citing works
Contreras, C., González, F., Fernø, J., Diéguez, C., Rahmouni, K., Nogueiras, R., & López, M. (2014) · Annals of Medicine · doi:10.3109/07853890.2014.919727 · Cited by 163 · see citing works
Free radicals and male reproduction.
Agarwal, A. K., & Allamaneni, S. S. R. (2011) · PubMed · Cited by 154 · see citing works
Irisin as a muscle-derived hormone stimulating thermogenesis – A critical update
Hofmann, T., Elbelt, U., & Stengel, A. (2014) · Peptides · doi:10.1016/j.peptides.2014.01.016 · Cited by 162 · see citing works
Fox, J., Rioux, B. V., Goulet, E. D. B., Johanssen, N. M., Swift, D. L., Bouchard, D. R., Loewen, H., & Sénéchal, M. (2018) · Scandinavian Journal of Medicine & Science in Sports · doi:10.1111/sms.12904 · Cited by 161 · see citing works
Crujeiras, A. B., Pardo, M., Roca-Rivada, A., Navas‐Carretero, S., Zulet, M. Á., Martínez, J. A., & Casanueva, F. F. (2013) · American Journal of Human Biology · doi:10.1002/ajhb.22493 · Cited by 153 · see citing works
Physical 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 157 · see citing works
Crujeiras, A., Zulet, M. D. L. Á., Lopez-Legarrea, P., de la Iglesia, R., Pardo, M., Carreira, M., Martinez, J., & Casanueva, F. (2014) · Metabolism: Clinical and Experimental · doi:10.1016/j.metabol.2013.12.007 · Cited by 143 · see citing works
Miyamoto-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 · see citing works
Rachid, 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 140 · see citing works
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 143 · see citing works
Chronic 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 · see citing works
Rodrı́guez, 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 · see citing works
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 128 · see citing works
Effects and underlying mechanisms of irisin on the proliferation and apoptosis of pancreatic β cells
Liu, S.-W., Du, F., Li, X., Wang, M.-M., Duan, R., Zhang, J.-X., Wu, Y., & Zhang, Q. (2017) · PLoS ONE · doi:10.1371/journal.pone.0175498 · Cited by 138 · see citing works
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 127 · see citing works
Irisin: 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 123 · see citing works
Circulating 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 120 · see citing works
Aydın, 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 · see citing works
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 · see citing works
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 118 · see citing works
Novelle, M. G., Contreras, C., Romero, A., López, M., & Diéguez, C. (2013) · International Journal of Endocrinology · doi:10.1155/2013/746281 · Cited by 117 · see citing works
Tsai, 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 117 · see citing works
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 116 · see citing works
Gamas, L., Matafome, P., & Seiça, R. (2015) · Journal of Diabetes Research · doi:10.1155/2015/359159 · Cited by 114 · see citing works
Dasarathy, 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 113 · see citing works
Relationship 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 · see citing works
Circulating 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 111 · see citing works
Irisin 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 111 · see citing works
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 111 · see citing works
Asadi, Y., Gorjipour, F., Behrouzifar, S., & Vakili, A. (2018) · Neurochemical Research · doi:10.1007/s11064-018-2569-9 · Cited by 111 · see citing works
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 109 · see citing works
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 107 · see citing works
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 104 · see citing works
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 104 · see citing works
Crujeiras, A. B., Pardo, M., & Casanueva, F. F. (2014) · Clinical Endocrinology · doi:10.1111/cen.12627 · Cited by 103 · see citing works
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 · see citing works
Marcher, 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 101 · see citing works
Irisin, 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 102 · see citing works
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 97 · see citing works
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 92 · see citing works
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 89 · see citing works
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 91 · see citing works
García-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 89 · see citing works
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 · see citing works
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 94 · see citing works
Moreno, 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 88 · see citing works
Irisin, 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 · see citing works
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 92 · see citing works
Irisin, 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 · see citing works
Rocha‐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 86 · see citing works
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 85 · see citing works
- 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 › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Rehabilitation › 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
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 ›
Are you an author, or do you see a problem with this page? Request a review
