Cited by 788Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismPeroxisome Proliferator-Activated Receptors

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Irisin Is Expressed and Produced by Human Muscle and Adipose Tissue in Association With Obesity and Insulin Resistance

Moreno-Navarrete, José María, Ortega, Francisco, Serrano, Marta, Guerra, Ester, Pardo, Gerard, Tinahones, Francisco, Ricart, Wifredo, Fernández-Real, José Manuel·2013·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2012-2749

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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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Items 301–400 of 786

Irisin Pretreatment Protects Kidneys against Acute Kidney Injury Induced by Ischemia/Reperfusion via Upregulating the Expression of Uncoupling Protein 2
Zhang, R., Ji, J., Zhou, X.-S., & Li, R. (2020) · BioMed Research International · doi:10.1155/2020/6537371 · Cited by 30
“Recently, extensive evidence has suggested that irisin has anti-inflammatory [8, 19, 24], antiapoptotic [25], and antioxidative [8, 17, 20] effects in various pathophysiological processes.”
Background
Circulating levels of Irisin in obese individuals at genetic risk for Alzheimer’s disease: Correlations with amyloid-β, metabolic, and neurocognitive indices
Tsai, C., & Pai, M. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.113013 · Cited by 35
Association of Circulating Irisin Levels and the Characteristics and Prognosis of Coronary Artery Disease
Pan, J.-A., Zhang, H., Yu, Q., Zhang, J.-F., Wang, C.-Q., Gu, J., & Chen, K. (2021) · The American Journal of the Medical Sciences · doi:10.1016/j.amjms.2021.02.020 · Cited by 34
Crosstalk between fat tissue and muscle, brain, liver, and heart in obesity: cellular and molecular perspectives
Jia, Z., Wang, Z., Pan, H., Zhang, J., Wang, Q., Zhou, C., & Liu, J. (2024) · European journal of medical research · doi:10.1186/s40001-024-02176-w · Cited by 35
“In addition, irisin is also considered an adipokine [51, 52].”
Irisin plasma concentration in PCOS and healthy subjects is related to body fat content and android fat distribution
Pukajło, K., Łaczmański, Ł., Kolačkov, K., Kuliczkowska-Płaksej, J., Bolanowski, M., Milewicz, A., & Daroszewski, J. (2015) · Gynecological Endocrinology · doi:10.3109/09513590.2015.1065482 · Cited by 32
Plasma irisin is increased following 12 weeks of Nordic walking and associates with glucose homoeostasis in overweight/obese men with impaired glucose regulation
Korkmaz, A., Venojärvi, M., Wasenius, N., Manderoos, S., DeRuisseau, K. C., Gidlund, E., Heinonen, O. J., Lindholm, H. J., Aunola, S., Eriksson, J. G., et al. (2018) · European Journal of Sport Science · doi:10.1080/17461391.2018.1506504 · Cited by 32
“…with resting energy expenditure and negatively with daily physical activity (Pardo et al., 2014), although there is no agreement on the association between irisin level and BMI (Crujeiras et al., 2014; Huh et al., 2012; Moreno-Navarrete et al., 2013; Pardo et al., 2014; Stengel et al., 2013).”
BackgroundInfluential
Irisin as a mediator between obesity and vascular inflammation in Chinese children and adolescents
Yin, C., Hu, W. M., Wang, M., Lv, W., Jia, T., & Xiao, Y. (2019) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2019.09.025 · Cited by 34
Crosstalk between Irisin Levels, Liver Fibrogenesis and Liver Damage in Non-Obese, Non-Diabetic Individuals with Non-Alcoholic Fatty Liver Disease
Armandi, A., Rosso, C., Nicolosi, A., Caviglia, G. P., Abate, M. L., Olivero, A., D’Amato, D., Vernero, M., Gaggini, M., Saracco, G. M., et al. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11030635 · Cited by 32
“In fact, irisin seems to be involved in the regulation of IR, with conflicting results [21,22].”
Background
The Effect of Exercise Training on Irisin Secretion in Patients with Type 2 Diabetes: A Systematic Review
Vecchiato, M., Zanardo, E., Battista, F., Quinto, G., Bergia, C., Palermi, S., Duregon, F., Ermolao, A., & Neunhäeuserer, D. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm12010062 · Cited by 32
“To this should be added the great variability described in the literature regarding the concentration of circulating irisin in healthy humans, as different studies reported a wide-ranging variability using different measurement kits [7,34].”
Background
PGC-1 mediates the regulation of metformin in muscle irisin expression and function.
Yang, Z., Xu, C., Chen, Y., & Zhao, Q. (2015) · Europe PMC (PubMed Central) · Cited by 32
Irisinemia: A Novel Concept to Coin in Clinical Medicine?
Sanchis‐Gomar, F., & Pérez-Quilis, C. (2013) · Annals of Nutrition and Metabolism · doi:10.1159/000354090 · Cited by 31
Irisin
Elbelt, U., Hofmann, T., & Stengel, A. (2013) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e328363bc65 · Cited by 30
Vitamin D is associated with metabotropic but not neurotrophic effects of exercise in ovariectomized rats
Babaei, P., Shirkouhi, S. G., Hoseini, R., & Tehrani, B. S. (2017) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-017-0288-z · Cited by 31
“Irisin has been proposed to be secreted by myocytes and adipocytes during exercise [17, 55] and modulates energy expenditure [17] insulin resistance [17] and dyslipidemia [56, 57].”
Background
Reduced plasma level of irisin in first trimester as a risk factor for the development of gestational diabetes mellitus
Wang, P., Ma, H.-H., Hou, X., Song, L., Song, X.-L., & Zhang, J.-F. (2018) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2018.05.038 · Cited by 31
Irisin Serum Levels in Metabolic Syndrome Patients Treated with Three Different Diets: A Post-Hoc Analysis from a Randomized Controlled Clinical Trial
Osella, A. R., Colaianni, G., Correale, M., Pesole, P. L., Bruno, I., Buongiorno, C., Deflorio, V., Leone, C. M., Colucci, S. C., Grano, M., et al. (2018) · Nutrients · doi:10.3390/nu10070844 · Cited by 31
“However, studies prevalently performed in humans have yielded controversial data regarding the association of irisin with obesity, insulin resistance, glucose disorders [30,31], fat mass and BMI [32–35].”
Background
Circulating Irisin Levels in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis
Hu, J., Ke, Y., Wu, F., Liu, S., Ji, C., Zhu, X., & Zhang, Y. (2020) · Gastroenterology Research and Practice · doi:10.1155/2020/8818191 · Cited by 31
“They were the ﬁ rst to ﬁ nd that irisin was mainly produced by exercise in both mice and humans, and a small amount of irisin could be synthesized from the liver or secreted from the adipose tissue [5, 6].”
Irisin and Energy Metabolism and the Role of Irisin on Metabolic Syndrome
Aladag, T., Moğulkoç, R., & Baltacı, A. K. (2023) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557523666230411105506 · Cited by 30
Circulating irisin in patients with polycystic ovary syndrome: a meta-analysis
Cai, X., Qiu, S., Li, L., Zügel, M., Steinacker, J. M., & Schümann, U. (2017) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2017.10.114 · Cited by 31
Irisin physiology, oxidative stress, and thyroid dysfunction: What next?
Huh, J. Y., & Mantzoros, C. S. (2015) · Metabolism · doi:10.1016/j.metabol.2015.02.009 · Cited by 30
Irisin, physical activity and fitness status in healthy humans: No association under resting conditions in a cross-sectional study
Biniaminov, N., Bandt, S., Röth, A., Haertel, S., Neumann, R., & Bub, A. (2018) · PLoS ONE · doi:10.1371/journal.pone.0189254 · Cited by 29
Plasma Irisin Levels in Subjects with Type 1 Diabetes: Comparison with Healthy Controls
Tentolouris, A., Eleftheriadou, I., Tsilingiris, D., Anastasiou, I. A., Kosta, O. A., Mourouzis, I. S., Kokkinos, A. D., Pantos, C. I., Katsilambros, N. L., & Tentolouris, N. (2018) · Hormone and Metabolic Research · doi:10.1055/a-0748-6170 · Cited by 31
The saturated fatty acid palmitate induces insulin resistance through Smad3-mediated down-regulation of FNDC5 in myotubes
Guo, Q., Wei, X., Hu, H., Yang, D., Zhang, B., Fan, X., Liu, J., He, H., Oh, Y., Wu, Q., et al. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.10.077 · Cited by 30
The association of circulating irisin with metabolic risk factors in Chinese adults: a cross-sectional community-based study
Tang, L., Tong, Y., Zhang, F., Chen, G., Zhang, Y. C., Jobin, J., & Tong, N. (2019) · BMC Endocrine Disorders · doi:10.1186/s12902-019-0479-8 · Cited by 30
Association of Circulating Irisin Levels with Adiposity and Glucose Metabolic Profiles in a Middle-Aged Chinese Population: A Cross-Sectional Study
Zhang, R., Fu, T., Zhao, X., Qiu, Y., Hu, X., Shi, H., & Yin, X. L. (2020) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s275878 · Cited by 30
Fibronectin type III domain-containing 5 in cardiovascular and metabolic diseases: a promising biomarker and therapeutic target
Zhang, X., Hu, C., Wu, H., Ma, Z., & Tang, Q. (2020) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-00557-5 · Cited by 30
“showed that circulating irisin and FNDC5 gene expression in adipose tissue or muscle are significantly decreased in association with obesity [196].”
Background
Irisin: circulating levels in serum and its relation to gonadal axis
Luo, Y., Qiao, X., Xu, L., & Huang, G. (2022) · Endocrine · doi:10.1007/s12020-022-02981-5 · Cited by 30
“In healthy people and patients with early diabetes, irisin has generally been negatively associated with insulin levels [18, 72].”
Background
Effect of Exercise Interventions on Irisin and Interleukin-6 Concentrations and Indicators of Carbohydrate Metabolism in Males with Metabolic Syndrome
Makiel, K., Suder, A., Targosz, A., Maciejczyk, M., & Haim, A. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12010369 · Cited by 33
Irisin and the Metabolic Phenotype of Adults with Prader-Willi Syndrome
Hirsch, H. J., Gross, I., Pollak, Y., Eldar‐Geva, T., & Gross‐Tsur, V. (2015) · PLoS ONE · doi:10.1371/journal.pone.0136864 · Cited by 30
“Moreno-Navarette et al found that irisin levels were lower in obese and type 2 diabetic patients [25].”
Background
Effects of lifestyle modification and metformin on irisin and FGF 21 among HIV ‐infected subjects with the metabolic syndrome
Srinivasa, S., Wong, K., Fitch, K. V., Wei, J., Petrow, E., Cypess, A. M., Torriani, M., & Grinspoon, S. K. (2014) · Clinical Endocrinology · doi:10.1111/cen.12582 · Cited by 30
FNDC5 relates to skeletal muscle IGF-I and mitochondrial function and gene expression in obese men with reduced growth hormone
Srinivasa, S., Suresh, C., Mottla, J. L., Hamarneh, S. R., Irazoqui, J. E., Frontera, W. R., Torriani, M., Stanley, T. L., & Makimura, H. (2015) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2015.12.008 · Cited by 29
Impact of adipokines and myokines on fat browning
Rodríguez, A., Catalán, V., Ramírez, B., Unamuno, X., Portincasa, P., Gómez‐Ambrosi, J., Frühbeck, G., & Becerril, S. (2020) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-020-00736-2 · Cited by 31
“Irisin is not only secreted by skeletal muscle but also, to a lesser extent, by AT, with an important autocrine and endocrine function [93, 113].”
Background
Exercise‐Induced cytokines, diet, and inflammation and their role in adipose tissue metabolism
Al‐Ibraheem, A. M. T., Hameed, A. A. Z., Marsool, M. D. M., Jain, H., Prajjwal, P., Khazmi, I., Nazzal, R., Al-Najati, H. M. H., Al‐Zuhairi, B. H. Y. K., Razzaq, M., et al. (2024) · Health Science Reports · doi:10.1002/hsr2.70034 · Cited by 33
“23,24 3.1.7 | Fibroblast growth factor 21 The administration of FGF21 in murine subjects resulted in a notable decrease in the levels of leptin mRNA expression, whereas no significant impact was observed on the expression levels of adiponectin mRNA.”
BackgroundInfluential
Circulating IRAPe, Irisin, and IL-34 in Relation to Insulin Resistance in Patients With Type 2 Diabetes
Mostafa, T. M., El-Gharbawy, N. M., & Werida, R. H. (2021) · Clinical Therapeutics · doi:10.1016/j.clinthera.2021.05.003 · Cited by 29
From Exercise to Cognitive Performance: Role of Irisin
Pesce, M., Fratta, I. L., Paolucci, T., Grilli, A., Patruno, A., Agostini, F., Bernetti, A., Mangone, M., Paoloni, M., Invernizzi, M., et al. (2021) · Applied Sciences · doi:10.3390/app11157120 · Cited by 29
“We also considered the expression in the brain, due to the relevant role of irisin of CNS origin on cognitive functions.”
Alteration of maternal serum irisin levels in gestational diabetes mellitus
Ural, Ü. M., Şahin, S. B., Tekın, Y. B., Cüre, M. C., & Sezgin, H. (2016) · Ginekologia Polska · doi:10.5603/gp.2016.0013 · Cited by 28
Central irisin administration suppresses thyroid hormone production but increases energy consumption in rats
Tekin, S., Erden, Y., Özyalın, F., Etem, E. Ö., Çiğremiş, Y., Çolak, C., Tekedereli, İ., & Sandal, S. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.03.046 · Cited by 28
Nonalcoholic fatty liver disease and sarcopenia: pathophysiological connections and therapeutic implications
Fernández, T., Briceño, F. A. C., Espinosa‐Ramírez, M., García-Valdés, P., López‐Fuenzalida, A., Riquelme, A. J., Arab, J. P., Cabrera, D., Arrese, M. A., & Francisco Barrera, M. (2020) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2020.1810563 · Cited by 28
“Irisin expression in muscle and serum levels are reduced in obese subjects [89].”
Background
Hydrogen Sulfide Regulates Irisin and Glucose Metabolism in Myotubes and Muscle of HFD-Fed Diabetic Mice
Parsanathan, R., & Jain, S. K. (2022) · Antioxidants · doi:10.3390/antiox11071369 · Cited by 27
“Decreased circulating irisin concentrations and FNDC5 gene expression have been observed in the muscle of obese T2DM subjects [13].”
Background
Recombinant irisin induces weight loss in high fat DIO mice through increase in energy consumption and thermogenesis
Niranjan, S. B., Belwalkar, S. V., Tambe, S. M., Venkataraman, K., & Mookhtiar, K. A. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.08.112 · Cited by 26
The Usefulness of Diagnostic Panels Based on Circulating Adipocytokines/Regulatory Peptides, Renal Function Tests, Insulin Resistance Indicators and Lipid-Carbohydrate Metabolism Parameters in Diagnosis and Prognosis of Type 2 Diabetes Mellitus with Obesity
Komosińska‐Vassev, K., Gala, O. M., Olczyk, K., Jura-Półtorak, A., & Olczyk, P. (2020) · Biomolecules · doi:10.3390/biom10091304 · Cited by 26
“[54] study showed that plasma levels of irisin and the expression of the FNDC5 gene in muscle and fat tissue in obese patients with type 2 diabetes and obesity are reduced.”
Background
Comparative studies on the effects of high-fat diet, endurance training and obesity on Ucp1 expression in male C57BL/6 mice
Shirkhani, S., Marandi, S. M., Kazeminasab, F., Esmaeili, M., Ghaedi, K., Esfarjani, F., Shiralian-Esfahani, H., & Nasr‐Esfahani, M. H. (2018) · Gene · doi:10.1016/j.gene.2018.07.015 · Cited by 28
The modulatory effects of irisin on asprosin, leptin, glucose levels and lipid profile in healthy and obese male and female rats
Özcan, S., Ülker, N., Bulmuş, Ö., Yardımcı, A., Özcan, M., & Canpolat, S. (2020) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2020.1722706 · Cited by 27
Several Circulating Biomarkers for PCOS Diagnosis
Luo, P., Zhang, C., He, Y., Yang, G., Liu, H., & Li, L. (2019) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-1025-3711 · Cited by 25
FNDC5/Irisin: A New Protagonist in Acute Brain Injury
Tu, T., Peng, J., & Jiang, Y. Q. (2020) · Stem Cells and Development · doi:10.1089/scd.2019.0232 · Cited by 26
“…we present recent data to make a summary as follows: First, the serum Irisin in obese patients or in those with type 2 diabetes (T2D) is lower than those in normal population, while the level is positively related to the amount of fatty tissue and negatively related to hyperglycemia [54,75, 76].”
Involvement of the p62/Nrf2/HO-1 pathway in the browning effect of irisin in 3T3-L1 adipocytes
Tsai, Y.-C., Wang, C.-W., Wen, B.-Y., Hsieh, P., Lee, Y., Yen, M., & Cheng, P. (2020) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2020.110915 · Cited by 25
Serum irisin level, insulin resistance, and lipid profiles in patients with hidradenitis suppurativa: a case-control study
Özkur, E., Erdem, Y., Altunay, İ. K., Demіr, D., Dolu, N. Ç., Serin, E., & Çerman, A. A. (2020) · Anais Brasileiros de Dermatologia · doi:10.1016/j.abd.2020.04.009 · Cited by 25
Asprosin, a novel glucogenic adipokine: a potential therapeutic implication in diabetes mellitus
Hekım, M. G., Keleştemur, M. M., Bulmuş, F. G., Bılgın, B., Bulut, F., Gökdere, E., Ozdede, M. R., Keleştimur, H., Canpolat, S., & Özcan, M. (2021) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2021.1894178 · Cited by 27
The Controversial Role of Irisin in Clinical Management of Coronary Heart Disease
Ou-Yang, W.-L., Guo, B., Xu, F., Lin, X., Li, F., Shan, S., Wu, F., Wang, Y., Zheng, M.-H., Xu, Q.-S., et al. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.678309 · Cited by 25
Effects of 3.5 GHz radiofrequency radiation on ghrelin, nesfatin-1, and irisin level in diabetic and healthy brains
Bektaş, H., Algül, Ş., Altındağ, F., Yeğin, K., Akdağ, M. Z., & Daşdağ, S. (2022) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2022.102168 · Cited by 25
Crucial Regulatory Role of Organokines in Relation to Metabolic Changes in Non-Diabetic Obesity
Lőrincz, H., Somodi, S., Ratku, B., Harangi, M., & Paragh, G. (2023) · Metabolites · doi:10.3390/metabo13020270 · Cited by 26
CRISPRa‐based activation of Fgf21 and Fndc5 ameliorates obesity by promoting adipocytes browning
Zhu, H., Liu, D., Sui, M., Zhou, M., Wang, B., Qi, Q., Wang, T., Zhang, G., Wan, F., & Zhang, B. (2023) · Clinical and Translational Medicine · doi:10.1002/ctm2.1326 · Cited by 27
Adropin and irisin levels in relation to nutrition, body composition, and insulin resistance in patients with end-stage renal disease on chronic hemodialysis and peritoneal dialysis
Kałużna, M., Hoppe, K., Schwermer, K., Ibrahim, A. Y., Pawlaczyk, K., & Ziemnicka, K. (2016) · Polskie Archiwum Medycyny Wewnętrznej · doi:10.20452/pamw.3466 · Cited by 25
Exercise-Induced Circulating Irisin Level Is Correlated with Improved Cardiac Function in Rats
Seo, D. Y., Bae, J. H., Kim, T. N., Kwak, H., Kha, P. T., & Han, J. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17113863 · Cited by 26
“Irisin is released from the skeletal muscle [4] and adipose tissue [14,15] during exercise.”
Background
Irisin and Fibronectin Type III Domain-Containing 5 Responses to Exercise in Different Environmental Conditions
Bubak, M. P., Heesch, M., Shute, R. J., Dinan, N. E., Laursen, T. L., Salle, D. T. L., & Slivka, D. R. (2017) · International journal of exercise science · doi:10.70252/xkmw8211 · Cited by 24
“On the other end on the spectrum, obese and insulin resistant individuals have a decreased amount of irisin (23).”
Background
Abnormal irisin level in serum and endometrium is associated with metabolic dysfunction in polycystic ovary syndrome patients
Wang, W., Guo, Y. C., Zhang, X., & Zheng, J. (2018) · Clinical Endocrinology · doi:10.1111/cen.13805 · Cited by 24
Superiority of the Non-Glycosylated Form over the Glycosylated Form of Irisin in the Attenuation of Adipocytic Meta-Inflammation: A Potential Factor in the Fight against Insulin Resistance
Mazur-Biały, A. I. (2019) · Biomolecules · doi:10.3390/biom9090394 · Cited by 24
Irisin induces white adipose tissue browning in mice as assessed by magnetic resonance imaging
Chen, Y., Ding, J., Zhao, Y., Ju, S., Mao, H. Z., & Peng, X. (2021) · Experimental Biology and Medicine · doi:10.1177/15353702211006049 · Cited by 24
“Noteworthy, the previous studies found that irisin induced browning of sWAT, but the role of irisin in vWAT has been controversial.(25) Interestingly, our study detected that irisin could induce browning in eWAT, even though the morphological changes of visceral lipid droplets were not significant in NCD mice.”
A Bibliometric Analysis of the Literature on Irisin from 2012–2021
Liu, J., Qi, B., Gan, L., Shen, Y., & Zou, Y. F. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19106153 · Cited by 25
“found that irisin was produced in human preadipocytes and adipocytes and 3T3-L1 adipocytes, and irisin expression in human muscle was 200 times higher than that in adipose tissue; they also concluded that circulating irisin levels were n gatively ssociated with obesity and insulin resistance [20].”
Background
Updates on Molecular Targets and Epigenetic-Based Therapies for PCOS
Смирнов, В. В., Beeraka, N. M., Butko, D. Y., Nikolenko, V. N., Bondarev, S., Achkasov, E. E., Sinelnikov, M. Y., & Vikram, P. R. H. (2022) · Reproductive Sciences · doi:10.1007/s43032-022-01013-x · Cited by 25
Exercise and Metabolic Health: The Emerging Roles of Novel Exerkines
Yazgan, B., Türkel, İ., Özerkliğ, B., ATAKAN, M. M., Aktitiz, S., & Koşar, Ş. N. (2022) · Current Protein and Peptide Science · doi:10.2174/1389203723666220629163524 · Cited by 25
Pathophysiological changes of the liver-muscle axis in end-stage liver disease: what is the right target?
Hénin, G., Lanthier, N., & Dahlqvist, G. (2022) · Acta gastro-enterologica belgica · doi:10.51821/85.4.10899 · Cited by 26
Adipokines in Rheumatoid Arthritis: Emerging Biomarkers and Therapeutic Targets
Bilski, J., Schramm‐Luc, A., Szczepanik, M., Mazur-Biały, A. I., Bonior, J., Luc, K., Zawojska, K., & Szklarczyk, J. (2023) · Biomedicines · doi:10.3390/biomedicines11112998 · Cited by 28
“Irisin, a myokine originally thought to be exclusively produced by skeletal muscle, has recently been found to be released from adipose tissue as well [404] and in smaller amounts from the liver, bone, testes, pancreas, brain, spleen, heart, and stomach [405–407].”
Background
The Role of Irisin throughout Women’s Life Span
Barbagallo, F., Cannarella, R., Garofalo, V., Marino, M., Vignera, S. L., Condorelli, R. A., Tiranini, L., Nappi, R. E., & Calogero, A. E. (2023) · Biomedicines · doi:10.3390/biomedicines11123260 · Cited by 25
Mechanisms by which obesity regulates inflammation and anti-tumor immunity in cancer
Miracle, C. E., McCallister, C. L., Egleton, R. D., & Salisbury, T. B. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.150437 · Cited by 24
Does iris(in) bring bad news or good news?
Buscemi, S., Corleo, D., Buscemi, C., & Giordano, C. S. D. S. (2017) · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity · doi:10.1007/s40519-017-0431-8 · Cited by 24
“found a positive correlation between irisin concentrations and insulin-sensitivity [33].”
BackgroundResultInfluential
Exercise and Omentin: Their Role in the Crosstalk Between Muscle and Adipose Tissues in Type 2 Diabetes Mellitus Rat Models
de Castro, C. A., da Silva, K. A., Rocha, M. C., Sene‐Fiorese, M., Nonaka, K. O., Malavazi, I., Aníbal, F. D. F., & Duarte, A. C. G. D. O. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2018.01881 · Cited by 24
“between muscular and adipose tissue, and is essential for the maintenance of homeostasis (Moreno-Navarrete et al., 2013).”
Background
Irisin in idiopathic foetal growth restriction
Çağlar, M., Göksu, M., İsenlik, B. S., Yavuzcan, A., Yılmaz, M., Üstün, Y., Aydın, S., & Kumru, S. (2014) · Journal of Endocrinological Investigation · doi:10.1007/s40618-014-0078-5 · Cited by 23
Irisin Regulates the Functions of Hepatic Stellate Cells
Dong, H. N., Park, S. Y., Le, C. T., Choi, D.-H., & Cho, E.-H. (2020) · Endocrinology and Metabolism · doi:10.3803/enm.2020.658 · Cited by 24
“A few studies have reported a negative correlation between the expression of FNDC5, the precursor of irisin, and tumor necrosis factor-α (TNF-α), and a positive correlation with anti-inflammatory factor, IL-10 [33].”
Background
Associations of Circulating Irisin with FNDC5 Expression in Fat and Muscle in Type 1 and Type 2 Diabetic Mice
Jiang, S., Piao, L., Ma, E. B., Ha, H., & Huh, J. Y. (2021) · Biomolecules · doi:10.3390/biom11020322 · Cited by 25
“Whereas some studies have shown that irisin is positively correlated with BMI [12–16], others have reported the opposite relationship [17,18].”
BackgroundInfluential
Serum levels of irisin in postmenopausal women with osteoporotic hip fractures
Liu, K., Jing, P., Liu, Z., Wang, Y., Han, Z., Wang, Y., Zheng, Z., Wu, Y., Wang, T., Li, Y., et al. (2021) · Cytokine · doi:10.1016/j.cyto.2021.155708 · Cited by 23
Gonadal failure is associated with visceral adiposity in myotonic dystrophies
Passeri, E., Bugiardini, E., Sansone, V., Pizzocaro, A., Fulceri, C., Valaperta, R., Borgato, S., Costa, E., Bandera, F., Ambrosi, B., et al. (2015) · European Journal of Clinical Investigation · doi:10.1111/eci.12459 · Cited by 23
Effects of whole-body cryotherapy on 25-hydroxyvitamin D, irisin, myostatin, and interleukin-6 levels in healthy young men of different fitness levels
Śliwicka, E., Cisoń, T., Straburzyńska‐Lupa, A., & Pilaczyńska-Szczȩśniak, Ł. (2020) · Scientific Reports · doi:10.1038/s41598-020-63002-x · Cited by 23
Impact of testosterone treatment on circulating irisin in men with late-onset hypogonadism and metabolic syndrome
Assyov, Y. S., Gateva, A., Karamfilova, V., Gatev, T., Nedeva, I., Velikova, T. V., & Kamenov, Z. A. (2020) · The Aging Male · doi:10.1080/13685538.2020.1770721 · Cited by 24
“As adiposity has also been suggested to contribute to circulating irisin levels [43], it could also explain some of the discrepancies in the two studies.”
Result
Relation of serum irisin levels to obesity and non-alcoholic fatty liver disease
Ulualan, G., Kiraz, Z. K., & Kırel, B. (2022) · The Turkish Journal of Pediatrics · doi:10.24953/turkjped.2020.3003 · Cited by 22
Sex-dependent association between circulating irisin levels and insulin resistance in healthy adults
Jameel, F., Thota, R. N., Wood, L. G., Plunkett, B., & Garg, M. L. (2015) · Journal of Nutrition & Intermediary Metabolism · doi:10.1016/j.jnim.2015.10.001 · Cited by 22
Novel Molecules Regulating Energy Homeostasis: Physiology and Regulation by Macronutrient Intake and Weight Loss
Gavrieli, A., & Mantzoros, C. S. (2016) · Endocrinology and Metabolism · doi:10.3803/enm.2016.31.3.361 · Cited by 21
“A diverse array of metabolic actions has been associated with irisin levels [45-66].”
Mechanistic insights into the beneficial effects of curcumin on insulin resistance: Opportunities and challenges
Balakumar, P., Venkatesan, K., Khan, N. A., Raghavendra, N. M., Venugopal, V., Bharathi, D. R., & Fuloria, N. K. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103627 · Cited by 22
FNDC5 (irisin) gene and exceptional longevity: a functional replication study with rs16835198 and rs726344 SNPs
Sanchis‐Gomar, F., Garatachea, N., He, Z.-H., Pareja-Galeano, H., Fuku, N., Tian, Y., Arai, Y., Abe, Y., Murakami, H., Miyachi, M., et al. (2014) · AGE · doi:10.1007/s11357-014-9733-1 · Cited by 22
Myokines in Response to a Tournament Season among Young Tennis Players
Witek, K., Żurek, P., Żmijewski, P., Jaworska, J., Lipińska, P., Gmiat, A., Antosiewicz, J., & Ziemann, E. (2016) · BioMed Research International · doi:10.1155/2016/1460892 · Cited by 22
“Some data have shown that irisin is also secreted by adipose tissue [16, 17].”
Background
Serum irisin levels in patients with psoriasis
Baran, A. M., Myśliwiec, H., Kiluk, P., Świderska, M., & Flisiak, I. (2016) · Journal of Dermatological Treatment · doi:10.1080/09546634.2016.1254327 · Cited by 22
Effects of Dietary Macronutrient Composition on FNDC5 and Irisin in Mice Skeletal Muscle
de Macêdo, S. M., Lelis, D. D. F., Mendes, K. L., Fraga, C. A. D. C., Brandi, I., Feltenberger, J. D., Farias, L., Guimarães, A. L., de Paula, A. D., & Santos, S. H. D. S. (2017) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2016.0109 · Cited by 22
“12 8, 14, 15 Up to”
Circulating myokine levels in different stages of glucose intolerance
Park, K., Ahn, C. W., Park, J. S., Kim, Y.-S., & Nam, J. S. (2020) · Medicine · doi:10.1097/md.0000000000019235 · Cited by 22
The effects of exercise training associated with low-level laser therapy on biomarkers of adipose tissue transdifferentiation in obese women
Campos, R. M. D. S., Dâmaso, A. R., Masquio, D. C. L., Duarte, F. O., Sene‐Fiorese, M., de Aquino, A. E., Savioli, F. A., Quintiliano, P. C. L., Kravchychyn, A. C. P., Guimarães, L. I., et al. (2018) · Lasers in Medical Science · doi:10.1007/s10103-018-2465-1 · Cited by 22
“is in agreement with a previous study, where the researchers investigated the Bmetabolic inflexibility^ developed during the obesity [5], suggesting that the regulation of body mass has been associated with a relevant link that involves adipose and muscle tissues mechanisms, considered essential for homeostasis [55].”
Result
Serum Levels of Irisin Predict Cumulative Clinical Outcomes in Heart Failure Patients With Type 2 Diabetes Mellitus
Berezin, A. A., Lichtenauer, M., Boxhammer, E., Fushtey, I. M., & Berezin, A. Е. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.922775 · Cited by 22
Association of plasma fatty acid composition with plasma irisin levels in normal weight and overweight/obese children
Viitasalo, A., Ågren, J., Venäläinen, T. M., Pihlajamäki, J., Jääskeläinen, J., Korkmaz, A., Atalay, M., & Lakka, T. A. (2015) · Pediatric Obesity · doi:10.1111/ijpo.12062 · Cited by 21
“Recent observations suggest that irisin is also an adipokine (9,10) that is secreted”
Background
Irisin levels are associated with urotensin II levels in diabetic patients
He, W., Bai, Q., Lata, A., Tang, C., & Zhang, A. (2015) · Journal of Diabetes Investigation · doi:10.1111/jdi.12331 · Cited by 21
Wpływ gastrektomii rękawkowej na poziom irisiny w surowicy pacjentów z chorobliwą otyłością
Demirpençe, M., Yilmaz, H., Çolak, A., Yalçın, H., Toprak, B., Türkön, H., Uğurlu, L., & Aydın, C. (2016) · Endokrynologia Polska · doi:10.5603/ep.a2016.0029 · Cited by 21
“[34], our study revealed lower irisin levels in morbidly obese patients, with respect to control subjects.”
Result
High Irisin levels in nondiabetic HIV ‐infected males are associated with insulin resistance, nonalcoholic fatty liver disease, and subclinical atherosclerosis
Moreno, Ó., Reyes‐García, R., Muñoz‐Torres, M., Merino, E., Boix, V., Reus, S., Giner, L., Alfayate, R., García-Fontana, B., Sánchez–Payá, J., et al. (2018) · Clinical Endocrinology · doi:10.1111/cen.13800 · Cited by 21
Circulating Irisin Levels as a Marker of Osteosarcopenic-Obesity in Cushing’s Disease
Guarnotta, V., Prinzi, A., Pitrone, M., Pizzolanti, G., & Giordano, C. S. D. S. (2020) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s249090 · Cited by 22
Serum irisin and apelin levels and markers of atherosclerosis in patients with subclinical hypothyroidism
Yilmaz, H., Demirpençe, M., Çolak, A., Yurdakul, L., Akşit, M. Z., Türkön, H., Ekinci, F., Hasturk, A. G., & Yaşar, E. (2019) · Archives of Endocrinology and Metabolism · doi:10.20945/2359-3997000000106 · Cited by 20
“Irisin, the most recently identified adipomyokine, is the extracellular cleaved product of fibronectin type III domain-containing 5 (FDNC5) and is regulated by peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1 alpha (PGC1α) (5).”
BackgroundInfluential
Pathophysiological role of endogenous irisin against tumorigenesis and metastasis: Is it a potential biomarker and therapeutic?
Sumsuzzman, D. M., Jin, Y., Choi, J., Yu, J., Lee, T. H., & Hong, Y. (2019) · Tumor Biology · doi:10.1177/1010428319892790 · Cited by 20
FNDC5/irisin facilitates muscle−adipose−bone connectivity through ubiquitination-dependent activation of runt-related transcriptional factors RUNX1/2
He, X., Hua, Y., Li, Q., Zhu, W. P., Pan, Y., Yang, Y., Li, X., Wu, M., Wang, J., & Gan, X. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101679 · Cited by 21
“Moreover, the irisin level measured in adipose tissue extraction was strongly associated with FNDC5 gene transcription in both subcutaneous and visceral WAT (41).”
Background
Irisin/FNDC5 inhibits the epithelial–mesenchymal transition of epithelial ovarian cancer cells via the PI3K/Akt pathway
Zhu, T., Zhang, W., Zhang, Y., Lu, E., Liu, H., Liu, X., Yin, S., & Zhang, P. (2022) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-022-06427-1 · Cited by 20
“It is released from fibronectin type III domain-containing protein 5 (FNDC5), which is widely expressed in the human body, and can make white fat brown, promote energy consumption, and regulate energy metabolism [9].”
Background
The MRC1/CD68 Ratio Is Positively Associated with Adipose Tissue Lipogenesis and with Muscle Mitochondrial Gene Expression in Humans
Moreno‐Navarrete, J. M., Ortega, F. J., Gómez‐Serrano, M., García‐Santos, E., Ricart, W., Tinahones, F. J., Mingrone, G., Peral, B., & Fernández‐Real, J. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070810 · Cited by 21
“Recently, irisin has been proposed to mediate the beneficial effects of exercise on metabolism, inducing browning of subcutaneous adipocytes and increasing total body energy expenditure and resistance to obesity-associated insulin resistance [34,35].”
Background
Greek goddess or Greek myth: the effects of exercise on irisin/FNDC5 in humans
Atherton, P. J., & Phillips, B. E. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2013.265371 · Cited by 20
FNDC5 is produced in the stomach and associated to body composition
Barja-Fernández, S., Folgueira, C., Castelao, C., Al–Massadi, O., Bravo, S. B., García‐Caballero, T., Leis, R., Pardo, M., Casanueva, F. F., & Seoane, L. M. (2016) · Scientific Reports · doi:10.1038/srep23067 · Cited by 20
Immunohistochemical localization of irisin in skin, eye, and thyroid and pineal glands of the crested porcupine(Hystrix cristata)
Tarakçı, B. G., GİRGİN, A., Timurkaan, S., Yalçın, M., Gür, F. M., & Karan, M. (2016) · Biotechnic & Histochemistry · doi:10.1080/10520295.2016.1183820 · Cited by 20
Effect of Metformin Treatment on Insulin Resistance Markers, and Circulating Irisin in Women with Polycystic Ovarian Syndrome (PCOS)
Masaeli, A., Nayeri, H., & Mirzaee, M. (2019) · Hormone and Metabolic Research · doi:10.1055/a-0896-1130 · Cited by 20
“Furthermore, lower serum irisin levels have been reported in T2DM patients [13], gestational diabetes mellitus [14] and in overweight/obese people [15].”
Background
Circulating Irisin in Healthy Adults: Changes after Acute Exercise, Correlation with Body Composition, and Energy Expenditure Parameters in Cross-Sectional Study
Lagzdiņa, R., Rumaka, M., Gersone, G., & Tretjakovs, P. (2020) · Medicina · doi:10.3390/medicina56060274 · Cited by 22
“found lower levels of irisin in overweight and obese individuals [28].”
Background
Circulating irisin is linked to bone mineral density in geriatric Chinese men
Zhang, J., Huang, X., Yu, R., Wang, Y., & Gao, C. (2020) · Open Medicine · doi:10.1515/med-2020-0215 · Cited by 20

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)
ORCID: Ortega, Francisco
Serrano, Marta
Tinahones, Francisco
Ricart, Wifredo
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
DOI: 10.1210/jc.2012-2749
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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Irisin Is Expressed and Produced by Human Muscle and Adipose Tissue in Association With Obesity and Insulin Resistance

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