The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Irisin Is Expressed and Produced by Human Muscle and Adipose Tissue in Association With Obesity and Insulin Resistance
Abstract
CONTEXT: Recently irisin (encoded by Fndc5 gene) has been reported to stimulate browning and uncoupling protein 1 expression in sc adipose tissue of mice. OBJECTIVE: The objective of the study was to investigate FNDC5 gene expression in human muscle and adipose tissue and circulating irisin according to obesity, insulin sensitivity, and type 2 diabetes. DESIGN, PATIENTS, AND MAIN OUTCOME MEASURE: Adipose tissue FNDC5 gene expression and circulating irisin (ELISA) were analyzed in 2 different cohorts (n = 125 and n = 76); muscle FNDC5 expression was also evaluated in a subcohort of 34 subjects. In vitro studies in human preadipocytes and adipocytes and in induced browning of 3T3-L1 cells (by means of retinoblastoma 1 silencing) were also performed. RESULTS: In both sc and visceral adipose tissue, FNDC5 gene expression decreased significantly in association with obesity and was positively associated with brown adipose tissue markers, lipogenic, insulin pathway-related, mitochondrial, and alternative macrophage gene markers and negatively associated with LEP, TNFα, and FSP27 (a known repressor of brown genes). Circulating irisin and irisin levels in adipose tissue were significantly associated with FNDC5 gene expression in adipose tissue. In muscle, the FNDC5 gene was 200-fold more expressed than in adipose tissue, and its expression was associated with body mass index, PGC1α, and other mitochondrial genes. In obese participants, FNDC5 gene expression in muscle was significantly decreased in association with type 2 diabetes. Interestingly, muscle FNDC5 gene expression was significantly associated with FNDC5 and UCP1 gene expression in visceral adipose tissue. In men, circulating irisin levels were negatively associated with obesity and insulin resistance. Irisin was secreted from human adipocytes into the media, and the induction of browning in 3T3-L1 cells led to increased secreted irisin levels. CONCLUSIONS: Decreased circulating irisin concentration and FNDC5 gene expression in adipose tissue and muscle from obese and type 2 diabetic subjects suggests a loss of brown-like characteristics and a potential target for therapy.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“and possibly irisin, which is known to be downregulated by glucotoxic, lipotoxic [47,48], and inflammatory conditions [45].”
Citations
Cites
A 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
Cold-Activated Brown Adipose Tissue in Healthy Men
van Marken Lichtenbelt, W. D., Vanhommerig, J. W., Smulders, N. M., Drossaerts, J. M. A. F. L., Kemerink, G. J., Bouvy, N. D., Schrauwen, P., & Teule, G. J. J. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808718 · Cited by 3,452
Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human
Wu, J., Boström, P., Sparks, L. M., Li, Y., Choi, J. H., Giang, A.-H., Khandekar, M. J., Virtanen, K. A., Nuutila, P., Schaart, G., et al. (2012) · Cell · doi:10.1016/j.cell.2012.05.016 · Cited by 3,406
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
PPARγ Is Required for the Differentiation of Adipose Tissue In Vivo and In Vitro
Rosen, E. D., Sarraf, P., Troy, A. E., Bradwin, G., Moore, K. J., Milstone, D. S., Spiegelman, B. M., & Mortensen, R. M. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80211-7 · Cited by 2,081
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
Carey, A. L., Steinberg, G. R., Macaulay, S. L., Thomas, W. G., Holmes, A. G., Ramm, G., Prelovsek, O., Hohnen-Behrens, C., Watt, M. J., James, D. E., et al. (2006) · Diabetes · doi:10.2337/db05-1404 · Cited by 898
Role of Myokines in Exercise and Metabolism
Pedersen, B. K., Åkerström, T. C. A., Nielsen, A. R., & Fischer, C. P. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00080.2007 · Cited by 841
Bergman, R. N., Prager, R., Volund, A., & Olefsky, J. M. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112886 · Cited by 772
van den Beld, A. W., de Jong, F. H., Grobbee, D. E., Pols, H. A. P., & Lamberts, S. W. J. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.9.6825 · Cited by 618
Cited by
Sorted by citations
Adipose tissue browning and metabolic health
Bartelt, A., & Heeren, J. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.204 · Cited by 1,177
Kalinkovich, A., & Livshits, G. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.008 · Cited by 882
Skeletal muscle inflammation and insulin resistance in obesity
Wu, H., & Ballantyne, C. M. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88880 · Cited by 695
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
Norheim, F., Langleite, T. M., Hjorth, M., Holen, T., Kielland, A., Stadheim, H. K., Gulseth, H. L., Birkeland, K. I., Jensen, J., & Drevon, C. A. (2014) · The FEBS Journal · doi:10.1111/febs.12619 · Cited by 563
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. 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
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
“The only available report in this respect showed reduced adipose tissue Fndc5 mRNA in morbid obesity and T2D (Moreno-Navarrete et al. 2013).”
BackgroundResultInfluentialHuh, J. Y., Mougios, V., Kabasakalis, A., Fatouros, I., Siopi, A., Douroudos, I. I., Filippaios, A., Panagiotou, G., Park, K. H., & Mantzoros, C. S. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1437 · Cited by 363
“There are reports suggesting white adipose tissue as a source of irisin secretion (16, 34), but the exercise-induced burst in irisin is likely accounted for skeletal muscle release alone.”
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
Evidence against a Beneficial Effect of Irisin in Humans
Raschke, S., Elsen, M., Gassenhuber, J., Sommerfeld, M. R., Schwahn, U., Brockmann, B., Jung, R., Wisløff, U., Tjønna, A. E., Raastad, T., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073680 · Cited by 327
“The reported irisin levels in human blood samples [34–37] are in conflict to our notion that human FNDC5 is not translated into full-length protein due to the non-ATG start codon.”
BackgroundHuh, J. Y., Dincer, F., Mesfum, E., & Mantzoros, C. S. (2014) · International Journal of Obesity · doi:10.1038/ijo.2014.42 · Cited by 309
Inter-tissue communication in cancer cachexia
Argilés, J. M. A., Stemmler, B., López-Soriano, F. J., & Busquets, S. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0123-0 · Cited by 317
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 317
“Although irisin is primarily known as a myokine, it is also released from adipose tissue (18, 60), earning its name as an adipokine and mediating the beneficial metabolic effects of exercise (101).”
BackgroundInfluentialPekkala, 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).”
BackgroundMyokines and Adipokines: Involvement in the Crosstalk between Skeletal Muscle and Adipose Tissue
Li, F., Li, Y., Duan, Y., Hu, C.-A. A., Tang, Y., & Yin, Y. (2017) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2016.10.003 · Cited by 288
Rodríguez, 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
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
“In humans, irisin levels, and FNDC5 gene expression are decreased in obese and T2D individuals (105).”
Gonzalez-Gil, A. M., & Elizondo-Montemayor, L. (2020) · Nutrients · doi:10.3390/nu12061899 · Cited by 278
“Irisin Ob: ↑ [39]+; T2DM: ↓ [39]+ AE: ↑ (aerobic or resistance) [40]+ CE: ↓? (aerobic or resistance) [41]+ ↑ (via PGC-1α): cold-induced shivering [42], ↑AMP:ATP ratio (via AMPK-PGC-1α pathway), FGF21* [43], and METRNL (via ↑PGC-1α4)* [44] ↓: proinflammatory cytokines [45] (possibly via NF-kB-mediated inhibition of PGC…”
BackgroundPolyzos, 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
Three new players in energy regulation: Preptin, adropin and irisin
Aydın, S. (2014) · Peptides · doi:10.1016/j.peptides.2014.03.021 · Cited by 261
Xin, C., Liu, J., Zhang, J., Zhu, D., Wang, H., Xiong, L., Lee, Y., Ye, J., Lian, K., Xu, C., et al. (2016) · International Journal of Obesity · doi:10.1038/ijo.2015.199 · Cited by 248
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
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
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
Besse-Patin, A., Montastier, E., Vinel, C., Castan-Laurell, I., Louche, K., Dray, C., Daviaud, D., Mir, L., Marques, M.-A., Thalamas, C., et al. (2014) · International Journal of Obesity · doi:10.1038/ijo.2013.158 · Cited by 227
Myokines in insulin resistance and type 2 diabetes
Eckardt, K., Görgens, S. W., Raschke, S., & Eckel, J. (2014) · Diabetologia · doi:10.1007/s00125-014-3224-x · Cited by 234
Irisin, a Novel Myokine, Regulates Glucose Uptake in Skeletal Muscle Cells via AMPK
Lee, H. J., Lee, J. O., Kim, N., Kim, J. K., Kim, H. I., Lee, Y. W., Kim, S. J., Choi, J., Oh, Y., Kim, J. H., et al. (2015) · Molecular Endocrinology · doi:10.1210/me.2014-1353 · Cited by 224
Daskalopoulou, S. S., Cooke, A. B., Sandoval, Y.-H. G., Mutter, A. F., Filippaios, A., Mesfum, E. T., & Mantzoros, C. S. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0204 · Cited by 220
Irisin in patients with nonalcoholic fatty liver disease
Polyzos, S. A., Kountouras, J., Anastasilakis, A. D., Geladari, E. V., & Mantzoros, C. S. (2014) · Metabolism · doi:10.1016/j.metabol.2013.09.013 · Cited by 215
“are currently conflicting; briefly, some authors reported a positive correlation between circulating irisin levels and BMI [11,32,35], whereas others reported a negative correlation [31,33].”
BackgroundResultInfluentialPardo, 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
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 222
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
Mazur-Bialy, A. I., Pocheć, E., & Zarawski, M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040701 · Cited by 203
“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].”
BackgroundThe Interplay Between Bone and Glucose Metabolism
Cipriani, C., Colangelo, L., Santori, R., Renella, M., Mastrantonio, M., Minisola, S., & Pepe, J. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00122 · Cited by 202
“Irisin resistance has been postulated in diabetes, with a consequent theoretical loss of all these positive effects on bone mass and strength (12, 15).”
BackgroundLow brown adipose tissue activity in endurance-trained compared with lean sedentary men
Vosselman, M. J., Hoeks, J., Brans, B., Pallubinsky, H., Nascimento, E. B. M., van der Lans, A. A. J. J., Broeders, E. P. M., Mottaghy, F. M., Schrauwen, P., & van Marken Lichtenbelt, W. D. (2015) · International Journal of Obesity · doi:10.1038/ijo.2015.130 · Cited by 193
Crosstalk 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
Askari, H., Rajani, S. F., Poorebrahim, M., Haghi‐Aminjan, H., Raeis-Abdollahi, E., & Abdollahi, M. R. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.01.012 · Cited by 191
Sarcopenia – The search for emerging biomarkers
Kalinkovich, A., & Livshits, G. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.05.001 · Cited by 191
“Moreover, decreased circulating irisin concentrations and reduced expression of its structural gene, FNDC5, in muscle and adipose tissue were observed in obese and type-2 diabetic subjects (Liu et al., 2013; Moreno-Navarrete et al., 2013; Zhang et al., 2014).”
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 190
“Irisin, a myokine potentially induced by acute exercise that may increase energy expenditure and thus play an important role in obesity and metabolic disorders, has been proposed to be associated with correlates of metabolic disorders (11) and as a potential future therapeutic target (6).”
BackgroundResultInfluentialWu, M. V., Bikopoulos, G. J., Hung, S., & Ceddia, R. B. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.591008 · Cited by 187
The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction
Packer, M. (2025) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2025.06.055 · Cited by 213
FNDC5/Irisin: Physiology and Pathophysiology
Waseem, R., Shamsi, A., Mohammad, T., Hassan, M. I., Kazim, S. N., Chaudhary, A. A., Rudayni, H. A., Al-Zharani, M., Ahmad, F., & Islam, A. (2022) · Molecules · doi:10.3390/molecules27031118 · Cited by 180
“Prolonged exercise increases PGC1α expression mainly in the skeletal muscles and heart and improves various metabolic parameters, including AMPK activation, PGC1α phosphorylation, insulin sensitivity and signaling, and FNDC5 production, followed by the cleavage of FNDC5 to secrete irisin [15,16].”
BackgroundRole of irisin in physiology and pathology
Liu, S., Cui, F., Ning, K., Wang, Z., Fu, P., Wang, D., & Xu, H. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.962968 · Cited by 186
“In the development of obesity, the high level of irisin was probably derived from the increased in white adipose tissue (WAT) (25), as the expression of FNDC5/irisin was decreased in muscle tissues (26), as well as in brown adipose tissue and other tissues.”
BackgroundNew role of irisin in hepatocytes: the protective effect of hepatic steatosis in vitro
Park, M.-J., Kim, D.-I., Choi, J.-H., Heo, Y.-R., & Park, S.-H. (2015) · Cellular Signalling · doi:10.1016/j.cellsig.2015.04.010 · Cited by 168
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 168
“These studies have highlighted conflicting reports on changes in circulating irisin levels in patients with insulin resistance states such as obesity, type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM) (3, 5, 12, 17, 21, 22, 24, 28, 30).”
BackgroundInfluentialIrisin 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
“Lower irisin concentrations were observed in obese individuals and patients suffering from type 2 diabetes [25], chronic renal failure [26], and prolonged hypothyroidism [27].”
BackgroundResultIrisin, 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 170
“circulating irisin levels is associated with obesity and insulin resistance [56].”
BackgroundIrisin 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
Association of Serum Irisin with Metabolic Syndrome in Obese Chinese Adults
Yan, B., Shi, X., Zhang, H., Pan, L., Ma, Z., Liu, S., Liu, Y., Li, X., Yang, S., & Li, Z. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094235 · Cited by 165
“Circulating irisin was found to be significantly reduced in long-term [8], new onset [9] and undefined [10] type 2 diabetes patients compared with nondiabetic controls, which suggested either the diabetic state itself or the metabolic condition that caused progression to type 2 diabetes is accompanied by lower circula…”
BackgroundFox, 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
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 156
“…Biology A limitation of the current study and previous is that a wide range of circulating irisin levels have been reported (Choi et al., 2013; Huh et al., 2012; Moreno-Navarrete et al., 2013; Stengel et al., 2012; Zhang et al., 2013), even through a same study (Moreno-Navarrete et al., 2013).”
BackgroundIrisin Inhibits Hepatic Cholesterol Synthesis via AMPK-SREBP2 Signaling
Tang, H. W., Yu, R., Liu, S., Huwatibieke, B., Li, Z., & Zhang, W. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.02.041 · Cited by 152
“Circulating irisin was found to be reduced in obese human (Yan et al., 2014; Moreno-Navarrete et al., 2013; Duran et al., 2015; Hou et al., 2015) and rodents (Bilski et al.”
BackgroundCharacterization of the metabolic effects of irisin on skeletal muscle in vitro
Vaughan, R. A., Gannon, N. P., Barberena, M. A., Garcia‐Smith, R., Bisoffi, M., Mermier, C. M., Conn, C. A., & Trujillo, K. A. (2014) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12268 · Cited by 150
Crujeiras, A. B., Zulet, M. Á., Lopez‐Legarrea, P., de la Iglesia, R., Pardo, M., Carreira, M. C., Martínez, J. A., & Casanueva, F. F. (2013) · Metabolism · doi:10.1016/j.metabol.2013.12.007 · Cited by 149
“[28] Moreno-Navarrete JM, Ortega F, Serrano M, et al.”
BackgroundResultInfluentialMiyamoto-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
Sesti, G., Andreozzi, F., Fiorentino, T. V., Mannino, G. C., Sciacqua, A., Marini, M. A., & Perticone, F. (2014) · Acta Diabetologica · doi:10.1007/s00592-014-0576-0 · Cited by 145
“In fact, there is evidence that circulating irisin levels [12] or muscle FNDC5 gene expression [16] is inversely associated with age, and accordingly, an inverse association has been also observed in the present study (Table 2).”
BackgroundResultInfluentialRecent advances in the understanding and management of polycystic ovary syndrome
Rocha, A. L., Oliveira, F. R., Azevedo, R. C., Silva, V. A., Peres, T. M., Candido, A. L., Gomes, K. B., & Reis, F. M. (2019) · F1000Research · doi:10.12688/f1000research.15318.1 · Cited by 142
“The expression of irisin is positively associated with body mass index (BMI) and muscle mass, and irisin metabolism is abnormal in patients with type 2 diabetes or gestational diabetes 26 .”
BackgroundIrisin: A renaissance in metabolism?
Polyzos, S. A., Kountouras, J., Shields, K., & Mantzoros, C. S. (2013) · Metabolism · doi:10.1016/j.metabol.2013.04.008 · Cited by 131
Anastasilakis, A. D., Pοlyzos, S. A., Makras, P., Gkiomisi, A. I., Bisbinas, I., Katsarou, A., Filippaios, A., & Mantzoros, C. S. (2014) · Osteoporosis International · doi:10.1007/s00198-014-2673-x · Cited by 132
Gouni‐Berthold, I., Berthold, H. K., Huh, J. Y., Berman, R., Spenrath, N., Krone, W., & Mantzoros, C. S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072858 · Cited by 134
“found an association between FNDC5 expression in muscle and BMI in obese subjects [40].”
BackgroundChronic 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].”
BackgroundBlüher, S., Panagiotou, G., Petroff, D., Markert, J., Wagner, A., Klemm, T., Filippaios, A., Keller, A., & Mantzoros, C. S. (2014) · Obesity · doi:10.1002/oby.20739 · Cited by 137
“Circulating irisin has also been reported to be lower in patients with type 2 diabetes (33,36).”
BackgroundResultRodrı́guez, 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
“In line with the suggested protective role of the myokine irisin in the development of obesity, negative correlations of circulating irisin levels with the BMI have been reported in humans (Aydin et al. 2013, Choi et al. 2013, Moreno-Navarrete et al. 2013, Polyzos et al. 2014).”
BackgroundThe many roles of PGC-1α in muscle — recent developments
Chan, M. C., & Arany, Z. P. (2014) · Metabolism · doi:10.1016/j.metabol.2014.01.006 · Cited by 127
“Skeletal muscle FNDC5 expression and circulating irisin was found to be lower in obese patients [97], and there was an increase in serum irisin after acute exercise [98].”
BackgroundIrisin: 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
“Consistent with this view, some studies also found circulating irisin was positively correlated with fat mass in human [4,5,8-10,15,16].”
BackgroundResultInfluentialIrisin improves endothelial function in obese mice through the AMPK-eNOS pathway
Han, F., Zhang, S., Hou, N., Wang, D., & Sun, X. (2015) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00443.2015 · Cited by 122
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 125
“On the contrary, a recent study showed a negative correlation of HOMA-IR with circulating irisin levels in young girls suggesting that irisin secretion at an early age might delay the onset of obesity, insulin resistance, and T2DM (37), other studies reported that circulating irisin was positively correlated with insu…”
BackgroundResultInfluentialNatalicchio, A., Marrano, N., Biondi, G., Spagnuolo, R., Labarbuta, R., Porreca, I., Cignarelli, A., Bugliani, M., Marchetti, P., Perrini, S., et al. (2017) · Diabetes · doi:10.2337/db17-0002 · Cited by 122
“Adipose tissue also secretes irisin (25); however,;72% of circulating irisin is estimated to be released by skeletal muscle (1).”
BackgroundAydın, 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
“Since the development of DMT2 and CKD is often associated with insulin resistance, it has been suggested that irisin may play an important role in the pathology of insulinresistance related disorders while it may provide a novel therapeutic target for the treatment of metabolic diseases [18, 32, 35].”
BackgroundResultNovelle, M. G., Contreras, C., Romero, A., López, M., & Diéguez, C. (2013) · International Journal of Endocrinology · doi:10.1155/2013/746281 · Cited by 122
“Considering the association of DMT2 and cardiovascular disease, a role for irisin is also tempting to be speculated.”
BackgroundInfluentialLi, M., Yang, M., Zhou, X., Fang, X., Hu, W., Zhu, W., Wang, C., Liu, D., Li, S., Liu, H., et al. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-2544 · Cited by 115
“Briefly, while some authors support our findings with reports of a positive correlation between circulating irisin levels and BMI (13, 14, 16), others reported a negative correlation (10, 11).”
BackgroundResultConsitt, L. A., & Clark, B. C. (2018) · The Journal of Frailty & Aging · doi:10.14283/jfa.2017.33 · Cited by 122
“Irisin levels have been reported to be low in obese individuals and type 2 diabetics (51) and irisin has been shown to induce beige cell markers in adipocytes derived from WAT (35) providing convincing evidence that myostatin induced inhibition of this protein may adversely affect fat metabolism in older, obese adults.”
BackgroundBrown Adipose Tissue and Its Role in Insulin and Glucose Homeostasis
Maliszewska, K., & Kretowski, A. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041530 · Cited by 124
“Moreover, a previous study observed decreased circulating irisin concentrations and FNDC5 gene expression in adipose tissue and muscle from obese and T2D subjects, suggesting a loss of brown fat-like characteristics [159].”
BackgroundGamas, L., Matafome, P., & Seiça, R. (2015) · Journal of Diabetes Research · doi:10.1155/2015/359159 · Cited by 114
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
“Recent studies suggest that both muscle and adipose tissues may contribute to circulating irisin (Moreno-Navarrete et al., 2013; RocaRivada et al., 2013).”
BackgroundPark, H., Kim, H. C., Zhang, D., Yeom, H., & Lim, S.-K. (2018) · Endocrine · doi:10.1007/s12020-018-1814-y · Cited by 112
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 113
“In addition, accumulating data support the production of irisin by adipocytes, suggesting its dual role as a myokine and adipokine [22, 40].”
BackgroundAronis, K. N., Moreno, M., Pοlyzos, S. A., Moreno‐Navarrete, J. M., Ricart, W., Delgado, E., de la Hera, J., Sahin-Efe, A., Chamberland, J. P., Berman, R., et al. (2014) · International Journal of Obesity · doi:10.1038/ijo.2014.101 · Cited by 111
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 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
Connecting Myokines and Metabolism
Ahima, R. S., & Park, H. K. (2015) · Endocrinology and Metabolism · doi:10.3803/enm.2015.30.3.235 · Cited by 111
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
Effects of exercise on cellular and tissue aging
Carapeto, P. V., & Aguayo-Mazzucato, C. (2021) · Aging · doi:10.18632/aging.203051 · Cited by 107
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
Singhal, V., Lawson, E. A., Ackerman, K. E., Fazeli, P. K., Clarke, H., Lee, H., Eddy, K. T., Marengi, D. A., Derrico, N. P., Bouxsein, M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0100218 · Cited by 103
“One study reported lower irisin levels in patients with type 2 diabetes than controls of similar BMI, which may represent a failure of this physiological response leading to diabetes [31].”
BackgroundIrisin Levels During Pregnancy and Changes Associated With the Development of Preeclampsia
Garcés, M. F., Franco, J. J. P., Ruíz-Linares, C. E., Lozano, A. R., Poveda, N. E., Torres‐Sierra, A. L., Eslava-Schmalbach, J. H., Álzate, J. P., Sánchez, A. Y., Sánchez, E., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-4127 · Cited by 100
Understanding the brown adipocyte as a contributor to energy homeostasis
Chechi, K., Carpentier, A. C., & Richard, D. (2013) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2013.04.002 · Cited by 99
Lower irisin level in patients with type 2 diabetes mellitus: A case‐control study and meta‐analysis
Zhang, C., Ding, Z., Lv, G., Li, J., Zhou, P., & Zhang, J. (2014) · Journal of Diabetes · doi:10.1111/1753-0407.12256 · Cited by 98
“In contrast, MorenoNavarrete et al.(13) reported a negative correlation between irisin concentrations and BMI.”
BackgroundInfluentialLee, M. J., Lee, S. A., Nam, B. Y., Park, S., Lee, S., Ryu, H. J., Kwon, Y. E., Kim, Y. L., Park, K. S., Oh, H. J., et al. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.08.002 · Cited by 98
Serum Irisin Levels, Precocious Myocardial Infarction, and Healthy Exceptional Longevity
Emanuele, E., Minoretti, P., Pareja-Galeano, H., Sanchis‐Gomar, F., Garatachea, N., & Lucía, A. (2014) · The American Journal of Medicine · doi:10.1016/j.amjmed.2014.04.025 · Cited by 92
Palacios‐González, B., Vadillo‐Ortega, F., Polo‐Oteyza, E., Sánchez, T. S., Ancira‐Moreno, M., Romero‐Hidalgo, S., Meraz‐Cruz, N., & Antuna-Puente, B. (2015) · Obesity · doi:10.1002/oby.21029 · Cited by 96
“We observed a positive correlation of circulating irisin to BMI, with the highest levels among children with obesity, as per previous studies involving adults (6,15); and a tendency toward a decrease of irisin levels in children with obesity after the PAP, related to a decrease in body weight.”
BackgroundActivation and recruitment of brown adipose tissue as anti-obesity regimens in humans
Yoneshiro, T., & Saito, M. (2014) · Annals of Medicine · doi:10.3109/07853890.2014.911595 · Cited by 94
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
“this notion is strengthened by a previous observation of an association between FnDc5 expression levels in muscle and adipose tissue (Moreno-navarrete et al. 2013).”
BackgroundResultGuo, P., Jin, Z. Y., Wu, H., Li, X., Ke, J., Zhang, Z., & Zhao, Q. (2019) · Brain and Behavior · doi:10.1002/brb3.1425 · Cited by 92
Garneau, L., & Aguer, C. (2019) · Diabetes & Metabolism · doi:10.1016/j.diabet.2019.02.006 · Cited by 95
Metadata
- Authors
- Moreno-Navarrete, J. M., Ortega, F., Serrano, M., Guerra, E., Pardo, G., Tinahones, F., Ricart, W., & Fernández-Real, J. M.
- Affiliations
- Department of Diabetes, Endocrinology, and Nutrition (J.M.M.-N., F.O., M.S., E.G., G.P., W.R., J.M.-F.-R.), Hospital Dr. Josep Trueta de Girona, Spain, Institut d'Investigació Biomèdica de Girona, Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn) (CB06/03/010), and Instituto de Salud Carlos III, 17007 Girona, Spain, Department of Endocrinology and Nu
- Instituto de Salud Carlos III (ES)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2013-04-01
- Volume
- 98
- Issue
- 4
- Pages
- E769-E778
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2046500896
- Cited by
- 788
- References
- 23
- Citations by year
- 2026: 23 · 2025: 29 · 2024: 39 · 2023: 46 · 2022: 84 · 2021: 63 · 2020: 78 · 2019: 62 · 2018: 62 · 2017: 63 · 2016: 63 · 2015: 75 · 2014: 67 · 2013: 34
- FWCI
- 58.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- RISalud Institutional Health Repository of Andalucía (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- irisin, FNDC5, obesity, insulin resistance, type 2 diabetes, brown adipose tissue, adipose tissue browning, skeletal muscle, UCP1, PGC-1α, adipocytes, mitochondrial genes, macrophage markers, FSP27, retinoblastoma 1
- MeSH terms
- Adipose Tissue, Adult, Aged, Animals, Cells, Cultured, Diabetes Mellitus, Type 2, Female, Fibronectins, Humans, Insulin Resistance, Male, Middle Aged, Obesity, Gene Expression, Muscle, Skeletal, 3T3-L1 Cells, Mice, Genetic Association Studies
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
