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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.
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“and possibly irisin, which is known to be downregulated by glucotoxic, lipotoxic [47,48], and inflammatory conditions [45].”
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de Oliveira, M., Síbio, M. T. D., Mathias, L. S., Rodrigues, B. M., Sakalem, M. E., & Nogueira, C. R. (2020) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2020.110917 · Cited by 56
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“factors that are both secreted from skeletal muscle and measurable in the blood [17-19].”
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Relationships between serum irisin levels and metabolic parameters in Japanese patients with obesity
Fukushima, Y., Kurose, S., Shinno, H., Thu, H. C. T., Tamanoi, A., Tsutsumi, H., Hasegawa, T., Nakajima, T., & Kimura, Y. (2016) · Obesity Science & Practice · doi:10.1002/osp4.43 · Cited by 52
“Irisin is associated with glucose/lipid metabolism (2,4,6,7,10,13,14,17,18) and may prevent obesity and onset of diabetes (3).”
BackgroundInfluentialYan, J., Liu, H.-J., Guo, W., & Yang, J. (2017) · Joint Bone Spine · doi:10.1016/j.jbspin.2017.03.011 · Cited by 52
Serum irisin level in myocardial infarction patients with or without heart failure
El-Mottaleb, N. A. A., Galal, H. M., Maghraby, K., & Gadallah, A. I. (2019) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2018-0736 · Cited by 52
“Besides that, the marked negative correlations between irisin and both BMI and WHR and between irisin & both SBP & DBP in MI cases and those with ischemic HF were observed & were in agreement with Moreno-Navarrete et al. 2013; Hou et al. 2015 & Hwang et al. 2016.”
ResultSong, R., Zhao, X., Cao, R. Y., Liang, Y., Zhang, D., & Wang, R. (2020) · Gene · doi:10.1016/j.gene.2020.145209 · Cited by 55
Serum irisin levels and thyroid function—Newly discovered association
Ruchała, M., Zybek, A., & Szczepanek‐Parulska, E. (2014) · Peptides · doi:10.1016/j.peptides.2014.07.021 · Cited by 51
Hwang, Y., Jeon, W. S., Park, C., & Youn, B. (2016) · Cardiovascular Diabetology · doi:10.1186/s12933-015-0319-8 · Cited by 52
“With regard to glucose tolerance, circulating irisin was inversely correlated with the presence of pre-diabetes/T2D, independent of other well-known risk factors for T2D, including age, sex, BMI, waist circumference, systolic blood pressure, and atherogenic lipid profiles.”
BackgroundInfluentialN-Glycosylation is required for FDNC5 stabilization and irisin secretion
Nie, Y., & Liu, D. (2017) · Biochemical Journal · doi:10.1042/bcj20170241 · Cited by 50
Sarcopenia and cachexia: molecular mechanisms and therapeutic interventions
Wang, T., Zhou, D., & Hong, Z. (2025) · MedComm · doi:10.1002/mco2.70030 · Cited by 46
Tung, Y.-T., Chiang, P.-C., Chen, Y.-L., & Chien, Y.-W. (2020) · Molecules · doi:10.3390/molecules25153329 · Cited by 49
“Being overweight and obese are defined as values of the body mass index (BMI), calculated as the weight in kilograms divided by the square of the height in meters, of ≥25 and 30 kg/m2, respectively.”
BackgroundImpact of Exercise Intensity on Cerebral BDNF Levels: Role of FNDC5/Irisin
Leger, C., Quirié, A., Méloux, A., Fontanier, E., Chaney, R., Basset, C., Lemaire‐Ewing, S., Garnier, P. E., & Prigent‐Tessier, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25021213 · Cited by 58
“…the cleavage of the fibronectin type III protein domain containing 5 (FNDC5), a transmembrane protein that is under the control of the peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1 α ), a transcription factor induced in skeletal muscle in response to its contraction [15–17].”
BackgroundBilski, J., Mazur-Biały, A. I., Brzozowski, B., Magierowski, M., Jasnos, K., Krzysiek-Mączka, G., Urbańczyk, K., Ptak‐Belowska, A., Zwolinska-Wcislo, M. M., Mach, T., et al. (2015) · Mediators of Inflammation · doi:10.1155/2015/605071 · Cited by 49
Glucocorticoid receptor positively regulates transcription of FNDC5 in the liver
Kim, H. K., Jeong, Y. J., Song, I.-S., Noh, Y. H., Seo, K. W., Kim, M., & Han, J. (2017) · Scientific Reports · doi:10.1038/srep43296 · Cited by 50
Elizondo‐Montemayor, L., Mendoza-Lara, G., Gutierrez-DelBosque, G., Peschard-Franco, M., Nieblas, B., & García‐Rivas, G. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123727 · Cited by 49
“The correlation between irisin levels and FNDC5 expression in adipose tissue de onstrates a positive feedback mechanism for autocrine or paracrine production of irisin by adipose tissue, which further increases its capacity to metabolize glucose and fatty acids [3] (Figure 1).”
BackgroundIrisin Acts via the PGC-1α and BDNF Pathway to Improve Depression-like Behavior
Jo, D., & Song, J. (2021) · Clinical Nutrition Research · doi:10.7762/cnr.2021.10.4.292 · Cited by 49
“Since irisin plays a role in biological responses, it also contributes to the pathological process in chronic kidney disease [39], obesity [40], and type 2 diabetes mellitus [41].”
BackgroundZhang, X., Tian, Y., Zhang, H., Kavishwar, A., Lynes, M. D., Brownell, A., Sun, H., Tseng, Y., Moore, A. V., & Ran, C. (2015) · Scientific Reports · doi:10.1038/srep13116 · Cited by 48
“This cell line has been widely used for studies of both WAT 7,8,60 and BAT, since these cells can be induced into both tissues 60–63 .”
MethodFNDC 5 could be regulated by leptin in adipose tissue
Gutiérrez‐Repiso, C., García‐Serrano, S., Rodríguez‐Pacheco, F., García‐Escobar, E., Haro‐Mora, J. J., García-Arnés, J. A., Valdés, S., Gonzalo, M., Soriguer, F., Moreno‐Ruiz, F. J., et al. (2014) · European Journal of Clinical Investigation · doi:10.1111/eci.12324 · Cited by 48
The relationships of irisin with bone mineral density and body composition in PCOS patients
Gao, S., Cheng, Y., Zhao, L., Chen, Y., & Liu, Y. (2015) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2767 · Cited by 48
“Of note, stimulation of browning on adipocytes may enhance irisin production [12], and then the abnormal brown fat distribution in PCOS patient accounts for the decreasing secretion of irisin.”
BackgroundBaştu, E., Zeybek, Ü., Gürevin, E. G., Yüksel, B., Çelik, F., Okumus, N. K., Demiral, İ., Dural, Ö., Celik, C., Bulut, H., et al. (2017) · Reproductive Sciences · doi:10.1177/1933719117711264 · Cited by 47
“Other studies have shown that serum irisin levels are negatively associated with insulin resistance and sensitivity.(17,20) In the present study, exercise and exogenous administration of irisin increased serum irisin levels.”
BackgroundIrisin treatment improves healing of dystrophic skeletal muscle
Reza, M. M., Sim, C. M., Subramaniyam, N., Ge, X., Sharma, M., Kambadur, R., & McFarlane, C. (2017) · Oncotarget · doi:10.18632/oncotarget.21636 · Cited by 45
“Irisin is a novel exercise-induced myokine and to date the role of Irisin on adipose tissue [16] and in type II diabetes [17, 18] has been researched extensively.”
BackgroundDünnwald, T., Melmer, A., Gatterer, H., Salzmann, K., Ebenbichler, C. F., Burtscher, M., Schobersberger, W., & Grander, W. (2019) · International Journal of Sports Medicine · doi:10.1055/a-0828-8047 · Cited by 47
“On the other hand, negative correlations between irisin levels and HOMA-IR, fasting blood glucose and BMI [33] or with insulin resistance [21] were shown in patients with type 2 diabetes or in obese subjects, respectively.”
BackgroundEffects of Body Weight Reduction on Serum Irisin and Metabolic Parameters in Obese Subjects
Fukushima, Y., Kurose, S., Shinno, H., Thu, H. C. T., Takao, N., Tsutsumi, H., Hasegawa, T., Nakajima, T., & Kimura, Y. (2016) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2016.40.5.386 · Cited by 46
“Secretion of irisin is higher from white adipose tissues in diet-induced obese rats compared to lean control rats [41], and some studies in humans have also found a positive correlation of the serum irisin level with fat [4,28,38,42-44].”
BackgroundBuscemi, S., Corleo, D., Vasto, S., Buscemi, C., Massenti, M. F., Nuzzo, D., Lucisano, G., Barile, A. M., Rosafio, G., Maniaci, V., et al. (2017) · International Journal of Obesity · doi:10.1038/ijo.2017.255 · Cited by 49
Irisin is a predictor of sarcopenic obesity in type 2 diabetes mellitus
Oğuz, A., Şahin, M., Tüzün, D., Kurutaş, E. B., Ülgen, C., Bozkus, O., & Gül, K. (2021) · Medicine · doi:10.1097/md.0000000000026529 · Cited by 46
“Multiple logistic regression tistically significant. gait speed, HGS = hand grip strength, OR = odds ratio, Total-C = total cholesterol. levels were negatively correlated with BMI, WHR, and FM.[42] Furthermore, a positive correlation has been reported between irisin levels and muscle mass and strength in humans and a…”
BackgroundInfluentialIrisin, Energy Homeostasis and Male Reproduction
Sengupta, P., Dutta, S., Karkada, I. R., Akhigbe, R. E., & Chinni, S. V. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.746049 · Cited by 46
Yang, M., Chen, P., Jin, H., Xie, X., Gao, T., Yang, L., & Yu, X. (2014) · Diabetology & Metabolic Syndrome · doi:10.1186/1758-5996-6-133 · Cited by 46
“Accordingly, circulating irisin has shown a positive correlation with insulin sensitivity in a cohort of male subjects without T2DM [14], suggesting a beneficial role of irisin in glucose homeostasis.”
BackgroundLower levels of irisin in patients with type 2 diabetes mellitus: A meta-analysis
Song, R., Zhao, X., Zhang, D., Wang, R., & Feng, Y. (2021) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2021.108788 · Cited by 45
The Physiological Role of Irisin in the Regulation of Muscle Glucose Homeostasis
Yano, N., Zhao, Y., & Zhao, T. C. (2021) · Endocrines · doi:10.3390/endocrines2030025 · Cited by 46
Komolka, K., Albrecht, E., Schering, L., Brenmoehl, J., Hoeflich, A., & Maak, S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0088060 · Cited by 44
“This is in line with results in humans, mice and rats [3,17,30].”
ResultModulation of Irisin and Physical Activity on Executive Functions in Obesity and Morbid obesity
Fagundo, A. B., Jiménez‐Múrcia, S., Giner‐Bartolomé, C., Agüera, Z., Sauchelli, S., Pardo, M., Crujeiras, A. B., Granero, R., Baños, R., Botella, C., et al. (2016) · Scientific Reports · doi:10.1038/srep30820 · Cited by 46
Zhang, L., Xie, Q., Tang, C., & Zhang, A. (2017) · Clinical and Experimental Hypertension · doi:10.1080/10641963.2016.1273945 · Cited by 44
“According to previous studies, UII may aggravate insulin resistant (11, 16), while irisin may improve insulin resistant (1, 17).”
BackgroundMethodKazeminasab, F., Sadeghi, E., & Afshari-Safavi, A. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/8235809 · Cited by 43
“First, recent studies have shown that irisin is not only a myokine released from skeletal muscle but also released from adipose tissue and is known as an adipokine [36, 37].”
Implications of circulating irisin and Fabp4 levels in patients with polycystic ovary syndrome
Abalı, R., Yüksel, İ. T., Yüksel, M. A., Bulut, B., İmamoğlu, M., Emirdar, V., Ünal, F., Güzel, S., & Celik, C. (2016) · Journal of Obstetrics and Gynaecology · doi:10.3109/01443615.2016.1174200 · Cited by 43
Zhang, L., Fang, X., Li, L., Liu, R., Zhang, C., Liu, H., Tan, M., & Yang, G. (2018) · Journal of Endocrinological Investigation · doi:10.1007/s40618-018-0902-4 · Cited by 43
Abedpoor, N., Taghian, F., Ghaedi, K., Niktab, I., Safaeinejad, Z., Rabiee, F., Tanhaei, S., & Nasr‐Esfahani, M. H. (2018) · Nutrition & Metabolism · doi:10.1186/s12986-018-0298-3 · Cited by 43
“Recent studies revealed substantial role of fibronectin type III domain containing 5 (FNDC5) and its secretory type, irisin, in energy metabolism and regulation [12, 13].”
BackgroundKolodziejski, P. A., Pruszyńska‐Oszmałek, E., Wojciechowicz, T., Sassek, M., Leciejewska, N., Jasaszwili, M., Billert, M., Małek, E., Szczepankiewicz, D., Misiewicz-Mielnik, M., et al. (2021) · Genes · doi:10.3390/genes12050756 · Cited by 46
“Later research also demonstrated that irisin is expressed and produced by human muscle cells [60].”
BackgroundPervin, S., Reddy, S. T., & Singh, R. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.653179 · Cited by 42
“Cold activation and physical activity among several other factors are known to alter the level of circulating irisin (97, 98).”
BackgroundAl‐Daghri, N. M., Mohammed, A. K., Al-Attas, O. S., Amer, O. E., Clerici, M., Alenad, A. M. H., & Alokail, M. S. (2016) · Lipids in Health and Disease · doi:10.1186/s12944-016-0224-5 · Cited by 42
“However, most of the previous studies in humans reported lower irisin levels in T2DM patients [12, 16, 24, 27], although these findings were contradicted by other investigations [11, 28].”
BackgroundResultShi, X., Lin, M., Liu, C., Xiao, F., Liu, Y., Huang, P., Zeng, X. Y., Yan, B., Liu, S., Li, X., et al. (2016) · BMC Endocrine Disorders · doi:10.1186/s12902-016-0123-9 · Cited by 43
“We did not find any direct effect of serum irisin on either fasting glucose or adiposity, which was also in line with many previous studies [8, 32].”
ResultThe association between serum irisin levels and cardiovascular disease in diabetic patients
Khorasani, Z. M., Bagheri, R. K., Yaghoubi, M. A., Chobkar, S., Aghaee, M. A., Abbaszadegan, M. R., & Sahebkar, A. (2018) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2018.11.050 · Cited by 42
Liu, Y., Fu, Y., Liu, Z., Shu, S.-Q., Wang, Y., Cai, J., Tang, C.-Y., & Dong, Z. (2020) · Biochimica et Biophysica Acta - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165792 · Cited by 35
Yang, S., Xiao, F., Pan, L., Zhang, H., Ma, Z., Liu, S., Liu, Y., Zhang, W., Zeng, X. Y., Liu, C., et al. (2015) · BMC Nephrology · doi:10.1186/s12882-015-0009-5 · Cited by 41
“Because low serum irisin was found to be associated with type 2 diabetes and obesity [15-17] and both these two conditions were independent risk factors of CKD [1], it is suspected that CKD patients have altered irisin levels.”
BackgroundIrisin as an early marker for predicting gestational diabetes mellitus: a prospective study
Erol, O. Ö., Erkal, N., Elli̇dağ, H. Y., İsenlik, B. S., Aydın, Ö., Derbent, A. U., & Yılmaz, N. (2016) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.3109/14767058.2016.1142967 · Cited by 41
“For the purpose of the study, controls were selected to match GDM cases with respect to maternal age, gestational age, and BMI at the time of the first prenatal visit.”
BackgroundInfluentialAssociation 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
The role of metabolic disorders in the pathogenesis of intrahepatic cholestasis of pregnancy
Menżyk, T., Bator, M., Derra, A., Kierach, R., & Kukla, M. (2018) · Clinical and Experimental Hepatology · doi:10.5114/ceh.2018.80122 · Cited by 41
“Obese and diabetic patients have significantly decreased serum irisin level [49].”
BackgroundIrisin 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
“Controversies remain in the relationship of irisin and obesity; in some studies elevated levels of irisin were determined in obese patients [24] whereas results with decreased levels in obese patients were demonstrated by others [25].”
ResultIrandoost, P., Alamdari, N. M., Saidpour, A., Shidfar, F., Roshanravan, N., Jafarabadi, M. A., Farsi, F., Hanjani, N. A., & Vafa, M. (2020) · Journal of Food Biochemistry · doi:10.1111/jfbc.13493 · Cited by 40
Muscle–Brain crosstalk in cognitive impairment
Han, X., Ashraf, M., Tipparaju, S. M., & Xuan, W. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1221653 · Cited by 43
“Myokines or cytokines released from skeletal muscle a ect neurons and inflammation in the brain: (1) detrimental factors: cathepsin B, myostatin, and GDF-15; (2) dual roles: IL-15, IL-6, LIF, and lactate; (3) beneficial factors: FNDC5, BDNF, IGF-1, and SPARC.”
BackgroundCirculating irisin is lower in gestational diabetes mellitus
Zhao, L., Li, J., Li, Z., Yang, J., Li, M., & Wang, G.-L. (2015) · Endocrine Journal · doi:10.1507/endocrj.ej15-0230 · Cited by 41
“But not all studies corroborate these findings [16].”
ResultAssociations 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
“Serum irisin levels were found to be reduced in long-term, new-onset and undefined diabetes as well as in metabolic syndrome (MetS) and in individuals with raised-FPG [20-23].”
BackgroundSugiyama, Y., Asai, K., Yamada, K., Kureya, Y., Ijiri, N., Watanabe, T., Kanazawa, H., & Hirata, K. (2017) · International Journal of COPD · doi:10.2147/copd.s126233 · Cited by 40
“8,9 10–12 According to recent reports, irisin has a protective effect against hyperglycemia-induced apoptosis in human vascular endothelial cells.”
BackgroundLeBlanc, D. R. B., Rioux, B. V., Cody, P., Moffatt, T. L., Kimber, D. E., Duhamel, T. A., Dolinsky, V. W., McGavock, J., & Sénéchal, M. (2017) · Physiological Reports · doi:10.14814/phy2.13539 · Cited by 40
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
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
Delgado, A. S. H., Roffe-Vazquez, D. N., González-Gil, A. M., Villarreal-Calderón, J. R., Tamez‐Rivera, O., Rodríguez-Gutiérrez, N. A., Castillo, E. C., Silva‐Platas, C., García‐Rivas, G., & Elizondo‐Montemayor, L. (2020) · Journal of Diabetes Research · doi:10.1155/2020/1949415 · Cited by 41
“In this regard, irisin, a novel adipomyokine secreted mainly by the skeletal muscle following acute bouts of exercise [16, 17], and to a lesser extent by adipose tissue, might contribute to these pathogenic changes [18, 19].”
BackgroundInfluentialAdipokines 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
Chedraui, P. A., & Pérez-López, F. R. (2013) · Climacteric · doi:10.3109/13697137.2013.802884 · Cited by 43
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
Factors associated with increased irisin levels in the type 1 diabetes mellitus
Ateş, İ., Arikan, M. F., Erdogan, K., Kaplan, M., Yuksel, M., Topçuoğlu, C., Yilmaz, N., & Guler, S. (2017) · Endocrine Regulations · doi:10.1515/enr-2017-0001 · Cited by 38
“Studies have shown that irisin levels were lower in the T2DM patients compared to the control ones (Choi et al. 2013; Moreno-Navarrete et al. 2013; Liu et al. 2014).”
ResultIrisin 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
Sene‐Fiorese, M., Duarte, F. O., de Aquino, A. E., Campos, R. M. D. S., Masquio, D. C. L., Tock, L., Duarte, A. C. G. D. O., Dâmaso, A. R., Parizotto, N. A., & Bagnato, V. S. (2015) · Lasers in Surgery and Medicine · doi:10.1002/lsm.22395 · Cited by 39
“These results were relevant once the regulation of body mass has been recognized as an important mechanism in the crosstalk between muscle and adipose tissue, being essential for the maintenance of homeostasis [32].”
BackgroundWang, L., Song, J., Wang, C., Lin, P., Liang, K., Sun, Y. S., He, T., Li, W., Zhao, R., Qin, J., et al. (2015) · Journal of Diabetes Research · doi:10.1155/2016/2616539 · Cited by 39
“Additionally, similar to what has been reported [25], we found that irisin is positively associated with insulin sensitivity (HOMA2-%S), even after controlling multiple covariates such as age, gender, BMI, blood lipids, antidiabetic medications, and the duration of diabetes.”
ResultAl‐Daghri, N. M., Alokail, M. S., Rahman, S., Amer, O. E., Al-Attas, O. S., Alfawaz, H., Tripathi, G., Sabico, S., Chrousos, G. P., McTernan, P. G., et al. (2015) · European Journal of Clinical Investigation · doi:10.1111/eci.12468 · Cited by 38
Wang, H.-H., Zhang, X., Chen, W.-K., Huang, Q., & Chen, Q.-Q. (2015) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2015.01.001 · Cited by 39
“The independent effect of decreased serum irisin levels and FNDC5 gene expression has been suggested to be a loss of brown-like characteristics and apotential target for therapy (Moreno-Navarrete et al., 2013).”
BackgroundCord blood irisin levels are positively correlated with birth weight in newborn infants
Joung, K. E., Park, K., Filippaios, A., Dincer, F., Christou, H. A., & Mantzoros, C. S. (2015) · Metabolism · doi:10.1016/j.metabol.2015.07.019 · Cited by 38
“In clinical settings, patients with type 2 diabetes mellitus have lower levels of irisin compared to healthy controls [3, 4], and irisin’s precursor, FNDC5, is decreased in patients with obesity [5].”
Backgroundİçli, A., Cüre, E., Cüre, M. C., Uslu, A. U., Balta, Ş., Arslan, Ş., Sakiz, D., & Küçük, A. (2016) · Journal of Investigative Medicine · doi:10.1136/jim-2015-000044 · Cited by 38
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
“Frontiers in Endocrinology 03 expressed a level of irisin almost hundred times lower than that of muscle (27, 43, 44).”
BackgroundAssociation between irisin and homocysteine in euglycemic and diabetic subjects
Alis, R., Sanchis‐Gomar, F., Pareja-Galeano, H., Mijares, A. H., Romagnoli, M., Víctor, V. M., & Rocha, M. (2014) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2014.08.017 · Cited by 37
Irisin, the metabolic syndrome and follistatin in humans
Boström, P., & Fernández‐Real, J. M. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.230 · Cited by 37
Irisin is a biomarker for metabolic syndrome in prepubertal children
Shim, Y. S., Kang, M. J., Yang, S., & Hwang, I. T. (2017) · Endocrine Journal · doi:10.1507/endocrj.ej17-0260 · Cited by 37
Calf Circumference as a Novel Tool for Risk of Disability of the Elderly Population
Sun, Y., Kao, T., Chang, Y., Fang, W., Wang, C.-C., Wu, L., Yang, H., Liaw, F., & Chen, W. (2017) · Scientific Reports · doi:10.1038/s41598-017-16347-9 · Cited by 37
Alsaawi, T. A., Aldisi, D. A., Abulmeaty, M. M. A., Khattak, M. N. K., Alnaami, A. M., Sabico, S., & Al‐Daghri, N. M. (2022) · Nutrients · doi:10.3390/nu14091855 · Cited by 37
“Irisin (ng/L) 169.1 ± 40.2 180.8 ± 44.3 145.8 ± 11.6 0.001 Note: Data presented as mean ± standard deviation; #denotes non-normal distribution and presented as median (inter-quartile range); BMI, body mass index; WHR, waist–hip ratio, MAC, mid-arm circumference; TSF, triceps skinfold-thickness; CI, conicity index; MAM…”
BackgroundInfluentialElizondo‐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
“Nonetheless, some studies have described lower irisin with increased weight or BMI [7, 22, 23].”
Liu, J., Yi, H., Liu, Y., & Chen, Y. (2019) · Medical Science Monitor · doi:10.12659/msm.917625 · Cited by 36
“Significantly lower levels of irisin were observed in patients with type 2 diabetes mellitus compared with non-diabetic individuals [32,33].”
BackgroundThe effects of intracerebroventricular infusion of irisin on feeding behaviour in rats.
Tekin, S., Erden, Y., Ozyalın, F., Çiğremiş, Y., Çolak, C., & Sandal, S. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.02.066 · Cited by 38
Muscle-dependent regulation of adipose tissue function in long-lived growth hormone-mutant mice
Li, X., Frazier, J., Spahiu, E., McPherson, M., & Miller, R. A. (2020) · Aging · doi:10.18632/aging.103380 · Cited by 34
Irisin regulates cardiac physiology in zebrafish
Sundarrajan, L., Yeung, C., Hahn, L., Weber, L. P., & Unniappan, S. (2017) · PLoS ONE · doi:10.1371/journal.pone.0181461 · Cited by 35
Tekin, 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
“It has been reported that there is an inverse relationship between serum irisin level and obesity, and that decreased irisin levels may lead to fat accumulation in the waist and hip (Moreno‐Navarrete 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
Association of Irisin and CRP Levels with the Radiographic Severity of Knee Osteoarthritis
Mao, Y., Xu, W., Xie, Z., & Dong, Q. (2015) · Genetic Testing and Molecular Biomarkers · doi:10.1089/gtmb.2015.0170 · Cited by 35
“In humans, serum irisin levels were found to be negatively correlated with body mass index (BMI) (Moreno-Navarrete et al. , 2013).”
InfluentialRejeki, P. S., Pranoto, A., Prasetya, R. E., & Sugiharto, S. (2021) · Comparative Exercise Physiology · doi:10.3920/cep200050 · Cited by 34
Relation of serum irisin level with metabolic and antropometric parameters in obese children
Çatlı, G., Küme, T., Tuhan, H., Anık, A., Çalan, Ö. G., Böber, E., & Abacı, A. (2016) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2016.07.019 · 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
Increased 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
“…associated with insulin resistance (Park et al. 2013; Crujeiras et al. 2014; Ebert et al. 2014; Sesti et al. 2014; Huh et al. 2016), others have shown decreased irisin in type 2 diabetic patients (Choi et al. 2013; Moreno-Navarrete et al. 2013; Hu et al. 2016) and rodents (Yang et al. 2015).”
BackgroundGonzález-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
“Studies with human-derived tissues have found a negative correlation between FNDC5 and leptin expression in SAT of adult subjects [54].”
Backgroundde Oliveira, M., Mathias, L. S., Rodrigues, B. M., Mariani, B. G., Graceli, J. B., Síbio, M. T. D., Olímpio, R. M. C., Moretto, F. C. F., Deprá, I. C., & Nogueira, C. R. (2020) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2020.110744 · Cited by 36
Irisin 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
Irisin and Secondary Osteoporosis in Humans
Zerlotin, R., Oranger, A., Pignataro, P., Dicarlo, M., Maselli, F., Mori, G., Colucci, S. C., Grano, M., & Colaianni, G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020690 · Cited by 34
“In the pediatric population, a reduction in irisin may play a role in the pathogenesis of childhood obesity [54] because this myokine plays a very important role in the regulation of adipose tissue metabolism [55,56] and correlates with glucose tolerance and insulin resistance in humans [57,58].”
BackgroundSerum irisin level is independent of sarcopenia and related muscle parameters in older adults
Baek, J. Y., Jang, I., Jung, H., Park, S. J., Lee, J. Y., Choi, E., Lee, Y. S., Lee, E., & Kim, B. (2022) · Experimental Gerontology · doi:10.1016/j.exger.2022.111744 · Cited by 39
Haghighi, A. H., hajinia, M., Askari, R., Abbasian, S., & Goldfied, G. (2022) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2021-0712 · 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
Ansari, S., Djalali, M., Honarvar, N. M., Mazaherioun, M., Zarei, M., Agh, F., Gholampour, Z., & Javanbakht, M. H. (2017) · Intern J Endocrinol Metab · doi:10.5812/ijem.40614 · Cited by 34
“showed that concentrations of irisin circulation and irisin gene expression in muscle and adipose tissue in patients with type 2 diabetes and obesity is reduced (25).”
BackgroundUsluoğullari, B., Usluoğulları, C. A., Balkan, F., & Örkmez, M. (2017) · Gynecological Endocrinology · doi:10.1080/09513590.2017.1284789 · Cited by 34
“Recent studies reported that irisin is also secreted by adipocytes [24].”
Background
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
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