{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T10:38:06Z","timestamp":1778323086018,"version":"3.51.4"},"reference-count":111,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Childhood cancer survivors (CCS) experience chronic health problems and significant metabolic burden. Timely identification of CCS at higher metabolic risk requires novel biomarkers. Irisin, a novel myokine\/adipokine has been associated with metabolic, bone and reproductive diseases, but its role in the health of CCS is unknown. The aim of this study was to examine irisin concentrations in children and adolescent CCS (vs. controls) and their association with metabolic, bone and hormonal parameters. Methods: Children and adolescent CCS, aged 8\u201318 years, as well as healthy controls, underwent a detailed physical, body composition, biochemical, hormonal and serum irisin assessment at least 6 months post-treatment. Results: A total of 59 children and adolescents (36 CCS, 23 controls; mean age \u00b1 SD 12.8 \u00b1 2.9 years; 10 prepubertal, 49 pubertal) participated in the study. Serum irisin concentrations (ng\/mL) were significantly lower in CCS than controls [median (IQR) 6.54 (4.12) vs. 11.70 (8.75) ng\/mL, respectively, p &lt; 0.001]. In the total study sample, serum irisin was correlated negatively with LH (rs = \u22120.314, p &lt; 0.05), CRP (rs = \u22120.366, p &lt; 0.005), age (rs = \u22120.323, p &lt; 0.05) and positively with ALP (rs = 0.328, p &lt; 0.05). Serum irisin was also positively correlated with ApoB and Lpa (rs = 0.410 and 0.421, respectively, p &lt; 0.05) in CCS, and with PTH (r = 0.542, p &lt; 0.005) in controls. Multivariate linear regression analysis indicated parathyroid hormone (PTH) as the only independent variable affecting irisin concentrations. Conclusions: Study results reinforce the irisin\u2013PTH interplay hypothesis. Future studies are needed to clarify the potential role of irisin as a bone biomarker of CCS in childhood and adolescence.<\/jats:p>","DOI":"10.3390\/jcm14145098","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T11:12:34Z","timestamp":1752837154000},"page":"5098","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Irisin Concentrations in Children and Adolescent Cancer Survivors and Their Relation to Metabolic, Bone, and Reproductive Profile: A Pilot Case\u2013Control Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Despoina","family":"Apostolaki","sequence":"first","affiliation":[{"name":"Center for Adolescent Medicine and UNESCO Chair in Adolescent Health Care, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Aghia Sophia Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katerina","family":"Katsibardi","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology-Oncology, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Aghia Sophia Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasiliki","family":"Efthymiou","sequence":"additional","affiliation":[{"name":"Center for Adolescent Medicine and UNESCO Chair in Adolescent Health Care, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Aghia Sophia Children\u2019s Hospital, 11527 Athens, Greece"},{"name":"University Research Institute for the Study of Genetic and Malignant Disorders in Childhood, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1634-701X","authenticated-orcid":false,"given":"Charikleia","family":"Stefanaki","sequence":"additional","affiliation":[{"name":"Center for Adolescent Medicine and UNESCO Chair in Adolescent Health Care, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Aghia Sophia Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6606-8647","authenticated-orcid":false,"given":"Aimilia","family":"Mantzou","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Diabetes, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Aghia Sophia Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stavroula","family":"Papadodima","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine and Toxicology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3098-5264","authenticated-orcid":false,"given":"George P.","family":"Chrousos","sequence":"additional","affiliation":[{"name":"University Research Institute for the Study of Genetic and Malignant Disorders in Childhood, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5178-0655","authenticated-orcid":false,"given":"Antonis","family":"Kattamis","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology-Oncology, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Aghia Sophia Children\u2019s Hospital, 11527 Athens, Greece"},{"name":"University Research Institute for the Study of Genetic and Malignant Disorders in Childhood, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1001-0926","authenticated-orcid":false,"given":"Flora","family":"Bacopoulou","sequence":"additional","affiliation":[{"name":"Center for Adolescent Medicine and UNESCO Chair in Adolescent Health Care, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Aghia Sophia Children\u2019s Hospital, 11527 Athens, Greece"},{"name":"University Research Institute for the Study of Genetic and Malignant Disorders in Childhood, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1007\/s13187-016-0997-2","article-title":"Who Is a Cancer Survivor? A Systematic Review of Published Definitions","volume":"32","author":"Marzorati","year":"2017","journal-title":"J. Cancer Educ."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1093\/jnci\/djad115","article-title":"Counts, incidence rates, and trends of pediatric cancer in the United States, 2003\u20132019","volume":"115","author":"Siegel","year":"2023","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1016\/S0140-6736(17)31610-0","article-title":"The cumulative burden of surviving childhood cancer: An initial report from the St Jude Lifetime Cohort Study (SJLIFE)","volume":"390","author":"Bhakta","year":"2017","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1001\/jama.2023.16875","article-title":"Clinical Care for People Who Survive Childhood Cancer: A Review","volume":"330","author":"Bhatia","year":"2023","journal-title":"Jama"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature10777","article-title":"A PGC1-\u03b1-dependent myokine that drives brown-fat-like development of white fat and thermogenesis","volume":"481","author":"Wu","year":"2012","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Roca-Rivada, A., Castelao, C., Senin, L.L., Landrove, M.O., Baltar, J., Bel\u00e9n Crujeiras, A., Seoane, L.M., Casanueva, F.F., and Pardo, M. (2013). FNDC5\/irisin is not only a myokine but also an adipokine. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060563"},{"key":"ref_8","first-page":"57","article-title":"Irisin as a Biomarker for Insulin Resistance in Polycystic Ovary Syndrome: A Meta-analysis","volume":"1","author":"Bacopoulou","year":"2020","journal-title":"J. Mol. Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1007\/s12020-017-1476-1","article-title":"Irisin in metabolic diseases","volume":"59","author":"Polyzos","year":"2018","journal-title":"Endocrine"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pinkowska, A., Podhorska-Oko\u0142\u00f3w, M., Dzi\u0119giel, P., and Nowi\u0144ska, K. (2021). The Role of Irisin in Cancer Disease. Cells, 10.","DOI":"10.3390\/cells10061479"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"197","DOI":"10.3109\/10520295.2014.977949","article-title":"Alteration of serum and cardiac tissue adropin, copeptin, irisin and TRPM2 expressions in DOX treated male rats","volume":"90","author":"Aydin","year":"2015","journal-title":"Biotech. Histochem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"He, W., Tang, Y., Li, C., Zhang, X., Huang, S., Tan, B., and Yang, Z. (2021). Exercise Enhanced Cardiac Function in Mice With Radiation-Induced Heart Disease via the FNDC5\/Irisin-Dependent Mitochondrial Turnover Pathway. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.739485"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Provatopoulou, X., Georgiou, G.P., Kalogera, E., Kalles, V., Matiatou, M.A., Papapanagiotou, I., Sagkriotis, A., Zografos, G.C., and Gounaris, A. (2015). Serum irisin levels are lower in patients with breast cancer: Association with disease diagnosis and tumor characteristics. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1898-1"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e0524","DOI":"10.1097\/MD.0000000000010524","article-title":"Serum irisin associates with breast cancer to spinal metastasis","volume":"97","author":"Zhang","year":"2018","journal-title":"Medicine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9850191","DOI":"10.1155\/2019\/9850191","article-title":"Serum Irisin Predicts Posthepatectomy Complications in Patients with Hepatocellular Carcinoma","volume":"2019","author":"Zhang","year":"2019","journal-title":"Dis. Markers"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"235","DOI":"10.5114\/ceh.2020.99517","article-title":"Serum concentrations of selected adipokines in virus-related liver cirrhosis and hepatocellular carcinoma","volume":"6","author":"Kukla","year":"2020","journal-title":"Clin. Exp. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhu, H., Liu, M., Zhang, N., Pan, H., Lin, G., Li, N., Wang, L., Yang, H., Yan, K., and Gong, F. (2018). Serum and Adipose Tissue mRNA Levels of ATF3 and FNDC5\/Irisin in Colorectal Cancer Patients With or Without Obesity. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.01125"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100529","DOI":"10.1016\/j.currproblcancer.2019.100529","article-title":"The diagnostic and prognostic roles of serum irisin in bladder cancer","volume":"44","author":"Esawy","year":"2020","journal-title":"Curr. Probl. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tsiani, E., Tsakiridis, N., Kouvelioti, R., Jaglanian, A., and Klentrou, P. (2021). Current Evidence of the Role of the Myokine Irisin in Cancer. Cancers, 13.","DOI":"10.3390\/cancers13112628"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.peptides.2016.12.014","article-title":"Increased FNDC5\/Irisin expression in human hepatocellular carcinoma","volume":"88","author":"Gaggini","year":"2017","journal-title":"Peptides"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1590\/s1677-5538.ibju.2017.0404","article-title":"The Diagnostic Value of FNDC5\/Irisin in Renal Cell Cancer","volume":"44","author":"Altay","year":"2018","journal-title":"Int. Braz. J. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.31557\/APJCP.2020.21.10.2847","article-title":"Circulating Irisin Levels and Redox Status Markers in Patients with Gastric Cancer: A Case-Control Study","volume":"21","author":"Shahidi","year":"2020","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"242","DOI":"10.3109\/10520295.2015.1136988","article-title":"Irisin immunohistochemistry in gastrointestinal system cancers","volume":"91","author":"Aydin","year":"2016","journal-title":"Biotech. Histochem."},{"key":"ref_24","first-page":"40","article-title":"Irisin immunostaining characteristics of breast and ovarian cancer cells","volume":"62","author":"Kuloglu","year":"2016","journal-title":"Cell Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.2147\/CMAR.S201979","article-title":"Comparison of irisin hormone expression between thyroid cancer tissues and oncocytic variant cells","volume":"11","author":"Ugur","year":"2019","journal-title":"Cancer Manag. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Nowinska, K., Jablonska, K., Pawelczyk, K., Piotrowska, A., Partynska, A., Gomulkiewicz, A., Ciesielska, U., Katnik, E., Grzegrzolka, J., and Glatzel-Plucinska, N. (2019). Expression of Irisin\/FNDC5 in Cancer Cells and Stromal Fibroblasts of Non-small Cell Lung Cancer. Cancers, 11.","DOI":"10.3390\/cancers11101538"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1002\/cncr.30628","article-title":"A prospective evaluation of clinical and genetic predictors of weight changes in breast cancer survivors","volume":"123","author":"Sadim","year":"2017","journal-title":"Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gil-Cosano, J.J., Ubago-Guisado, E., Llorente-Cantarero, F.J., Marmol-Perez, A., Rodriguez-Solana, A., Pascual-Gazquez, J.F., Mateos, M.E., Molina-Hurtado, J.R., Garcia-Fontana, B., and Narciso, P.H. (2024). Movement Behaviors and Bone Biomarkers in Young Pediatric Cancer Survivors: A Cross-Sectional Analysis of the iBoneFIT Project. Nutrients, 16.","DOI":"10.3390\/nu16223914"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/j.2047-6310.2012.00064.x","article-title":"Extended international (IOTF) body mass index cut-offs for thinness, overweight and obesity","volume":"7","author":"Cole","year":"2012","journal-title":"Pediatr. Obes."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004). The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics, 114, 555\u2013576.","DOI":"10.1542\/peds.114.2.S2.555"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_32","unstructured":"Lohman, T.J.R., and Martorell, R.A.F. (1998). Anthropometric Standardization Reference Manual, Human Kinetics."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Serdar, C.C., Cihan, M., Y\u00fccel, D., and Serdar, M.A. (2021). Sample size, power and effect size revisited: Simplified and practical approaches in pre-clinical, clinical and laboratory studies. Biochem. Med., 31.","DOI":"10.11613\/BM.2021.010502"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.diabres.2018.03.046","article-title":"High irisin levels are associated with better glycemic control and bone health in children with Type 1 diabetes","volume":"141","author":"Faienza","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/nrendo.2016.221","article-title":"Physiology and role of irisin in glucose homeostasis","volume":"13","author":"Perakakis","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1016\/j.metabol.2012.09.002","article-title":"FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise","volume":"61","author":"Huh","year":"2012","journal-title":"Metabolism"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1210\/jc.2014-2932","article-title":"Serum irisin levels are regulated by acute strenuous exercise","volume":"100","author":"Scheuermann","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"857270","DOI":"10.1155\/2014\/857270","article-title":"Association of irisin with fat mass, resting energy expenditure, and daily activity in conditions of extreme body mass index","volume":"2014","author":"Pardo","year":"2014","journal-title":"Int. J. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1210\/jc.2015-1208","article-title":"Irisin and its relation to insulin resistance and puberty in obese children: A longitudinal analysis","volume":"100","author":"Reinehr","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1507\/endocrj.EJ17-0260","article-title":"Irisin is a biomarker for metabolic syndrome in prepubertal children","volume":"65","author":"Shim","year":"2018","journal-title":"Endocr. J."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Singhal, V., Lawson, E.A., Ackerman, K.E., Fazeli, P.K., Clarke, H., Lee, H., Eddy, K., Marengi, D.A., Derrico, N.P., and Bouxsein, M.L. (2014). Irisin levels are lower in young amenorrheic athletes compared with eumenorrheic athletes and non-athletes and are associated with bone density and strength estimates. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100218"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.bone.2018.01.003","article-title":"Body fat mass, lean body mass and associated biomarkers as determinants of bone mineral density in children 6\u20138 years of age\u2014The Physical Activity and Nutrition in Children (PANIC) study","volume":"108","author":"Soininen","year":"2018","journal-title":"Bone"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Elizondo-Montemayor, L., Mendoza-Lara, G., Gutierrez-DelBosque, G., Peschard-Franco, M., Nieblas, B., and Garcia-Rivas, G. (2018). Relationship of Circulating Irisin with Body Composition, Physical Activity, and Cardiovascular and Metabolic Disorders in the Pediatric Population. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123727"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Esin, K., Batirel, S., \u00dclfer, G., Yigit, P., and Sanlier, N. (2023). Association of Serum Irisin Levels with Body Composition, Metabolic Profile, Leptin, and Adiponectin Levels in Lean and Obese Children. Medicina, 59.","DOI":"10.3390\/medicina59111954"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.jdiacomp.2013.03.002","article-title":"Lower circulating irisin is associated with type 2 diabetes mellitus","volume":"27","author":"Liu","year":"2013","journal-title":"J. Diabetes Complicat."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s13105-015-0400-5","article-title":"Circulating irisin and glucose metabolism in overweight\/obese women: Effects of \u03b1-lipoic acid and eicosapentaenoic acid","volume":"71","author":"Huerta","year":"2015","journal-title":"J. Physiol. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"124","DOI":"10.4274\/jcrpe.3963","article-title":"Serum Irisin and Oxytocin Levels as Predictors of Metabolic Parameters in Obese Children","volume":"9","author":"Binay","year":"2017","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.numecd.2018.04.009","article-title":"High irisin levels in overweight\/obese children and its positive correlation with metabolic profile, blood pressure, and endothelial progenitor cells","volume":"28","author":"Oliveira","year":"2018","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1016\/j.jdiacomp.2016.07.019","article-title":"Relation of serum irisin level with metabolic and antropometric parameters in obese children","volume":"30","author":"Tuhan","year":"2016","journal-title":"J. Diabetes Complicat."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1210\/js.2018-00399","article-title":"Fibroblast Growth Factor 21, Adiponectin, and Irisin as Markers of Unfavorable Metabolic Features in 12-Year-Old Children","volume":"3","author":"Tenhola","year":"2019","journal-title":"J. Endocr. Soc."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.metabol.2016.02.006","article-title":"Association between circulating irisin and insulin resistance in non-diabetic adults: A meta-analysis","volume":"65","author":"Qiu","year":"2016","journal-title":"Metabolism"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1007\/s00592-014-0576-0","article-title":"High circulating irisin levels are associated with insulin resistance and vascular atherosclerosis in a cohort of nondiabetic adult subjects","volume":"51","author":"Sesti","year":"2014","journal-title":"Acta Diabetol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/eci.12196","article-title":"Irisin as a predictor of glucose metabolism in children: Sexually dimorphic effects","volume":"44","author":"Alkharfy","year":"2014","journal-title":"Eur. J. Clin. Invest."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1002\/oby.20739","article-title":"Effects of a 1-year exercise and lifestyle intervention on irisin, adipokines, and inflammatory markers in obese children","volume":"22","author":"Panagiotou","year":"2014","journal-title":"Obesity"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"E769","DOI":"10.1210\/jc.2012-2749","article-title":"Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance","volume":"98","author":"Ortega","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.diabres.2013.01.007","article-title":"Serum irisin levels in new-onset type 2 diabetes","volume":"100","author":"Choi","year":"2013","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1016\/j.clinbiochem.2015.07.098","article-title":"Irisin levels in the progression of diabetes in sedentary women","volume":"48","author":"Duran","year":"2015","journal-title":"Clin. Biochem."},{"key":"ref_58","first-page":"6737318","article-title":"Association between Irisin, hs-CRP, and Metabolic Status in Children and Adolescents with Type 2 Diabetes Mellitus","volume":"2019","year":"2019","journal-title":"Mediat. Inflamm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1111\/1440-1681.12439","article-title":"Circulating irisin levels are associated with lipid and uric acid metabolism in a Chinese population","volume":"42","author":"Tang","year":"2015","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.metabol.2017.05.007","article-title":"Association of circulating irisin levels with metabolic and metabolite profiles of Korean adolescents","volume":"73","author":"Jang","year":"2017","journal-title":"Metabolism"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/j.metabol.2014.06.001","article-title":"Circulating irisin, omentin-1, and lipoprotein subparticles in adults at higher cardiovascular risk","volume":"63","author":"Panagiotou","year":"2014","journal-title":"Metabolism"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4899","DOI":"10.1210\/jc.2013-2373","article-title":"Circulating irisin in relation to insulin resistance and the metabolic syndrome","volume":"98","author":"Park","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Oelmann, S., Nauck, M., V\u00f6lzke, H., Bahls, M., and Friedrich, N. (2016). Circulating Irisin Concentrations Are Associated with a Favourable Lipid Profile in the General Population. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0154319"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1159\/000521265","article-title":"Circulating Irisin Levels in Preadolescents and Adolescents Born Preterm","volume":"94","author":"Koutroumpa","year":"2021","journal-title":"Horm. Res. Paediatr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3247","DOI":"10.1210\/jc.2014-1367","article-title":"Circulating irisin in healthy, young individuals: Day-night rhythm, effects of food intake and exercise, and associations with gender, physical activity, diet, and body composition","volume":"99","author":"Anastasilakis","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s40200-016-0239-5","article-title":"Association of circulating irisin levels with normal weight obesity, glycemic and lipid profile","volume":"15","author":"Mehrabian","year":"2015","journal-title":"J. Diabetes Metab. Disord."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Gouni-Berthold, I., Berthold, H.K., Huh, J.Y., Berman, R., Spenrath, N., Krone, W., and Mantzoros, C.S. (2013). Effects of lipid-lowering drugs on irisin in human subjects in vivo and in human skeletal muscle cells ex vivo. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072858"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.peptides.2012.11.014","article-title":"Circulating levels of irisin in patients with anorexia nervosa and different stages of obesity--correlation with body mass index","volume":"39","author":"Stengel","year":"2013","journal-title":"Peptides"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Mazur-Bialy, A.I., Poche\u0107, E., and Zarawski, M. (2017). Anti-Inflammatory Properties of Irisin, Mediator of Physical Activity, Are Connected with TLR4\/MyD88 Signaling Pathway Activation. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040701"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1385\/IR:30:3:261","article-title":"C-reactive protein: An activator of innate immunity and a modulator of adaptive immunity","volume":"30","author":"Mold","year":"2004","journal-title":"Immunol. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/j.jacc.2004.12.077","article-title":"The effects of physical activity on serum C-reactive protein and inflammatory markers: A systematic review","volume":"45","author":"Kasapis","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/cen.12658","article-title":"The relationship between circulating irisin levels and endothelial function in lean and obese subjects","volume":"83","author":"Hou","year":"2015","journal-title":"Clin. Endocrinol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/ijo.2017.255","article-title":"Factors associated with circulating concentrations of irisin in the general population cohort of the ABCD study","volume":"42","author":"Buscemi","year":"2018","journal-title":"Int. J. Obes."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"140","DOI":"10.3803\/EnM.2019.34.2.140","article-title":"Association between Circulating Irisin and C-Reactive Protein Levels: A Systematic Review and Meta-Analysis","volume":"34","author":"Eslampour","year":"2019","journal-title":"Endocrinol. Metab."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s12020-016-0913-x","article-title":"The role of sex, adiposity, and gonadectomy in the regulation of irisin secretion","volume":"54","author":"Qiu","year":"2016","journal-title":"Endocrine"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Scalzo, R.L., Peltonen, G.L., Giordano, G.R., Binns, S.E., Klochak, A.L., Paris, H.L., Schweder, M.M., Szallar, S.E., Wood, L.M., and Larson, D.G. (2014). Regulators of human white adipose browning: Evidence for sympathetic control and sexual dimorphic responses to sprint interval training. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090696"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e247","DOI":"10.1210\/clinem\/dgaa720","article-title":"Serum Irisin Levels in Central Precocious Puberty and Its Variants","volume":"106","author":"Kutlu","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1210\/jc.2013-4127","article-title":"Irisin levels during pregnancy and changes associated with the development of preeclampsia","volume":"99","author":"Peralta","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.anireprosci.2017.06.018","article-title":"Irisin stimulates gonadotropins gene expression in tilapia (Oreochromis niloticus) pituitary cells","volume":"185","author":"Jiang","year":"2017","journal-title":"Anim. Reprod. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1177\/1933719117711264","article-title":"Effects of Irisin and Exercise on Metabolic Parameters and Reproductive Hormone Levels in High-Fat Diet-Induced Obese Female Mice","volume":"25","author":"Bastu","year":"2018","journal-title":"Reprod. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1530\/REP-20-0072","article-title":"Irisin may have a role in pubertal development and regulation of reproductive function in rats","volume":"160","author":"Ulker","year":"2020","journal-title":"Reproduction"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.repbio.2017.05.011","article-title":"Reproductive effects of irisin: Initial in vitro studies","volume":"17","author":"Poretsky","year":"2017","journal-title":"Reprod. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1093\/humrep\/17.8.2016","article-title":"Ovarian response and pregnancy outcome related to mid-follicular LH levels in women undergoing assisted reproduction with GnRH agonist down-regulation and recombinant FSH stimulation","volume":"17","author":"Humaidan","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.fertnstert.2014.03.030","article-title":"Does prolonged pituitary down-regulation with gonadotropin-releasing hormone agonist improve the live-birth rate in in vitro fertilization treatment?","volume":"102","author":"Ren","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s12020-022-02981-5","article-title":"Irisin: Circulating levels in serum and its relation to gonadal axis","volume":"75","author":"Luo","year":"2022","journal-title":"Endocrine"},{"key":"ref_86","first-page":"37","article-title":"Obesity and polycystic ovary syndrome","volume":"40","author":"Naderpoor","year":"2015","journal-title":"Minerva Endocrinol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Luo, Y., Qiao, X., Ma, Y., Deng, H., Xu, C.C., and Xu, L. (2021). Irisin deletion induces a decrease in growth and fertility in mice. Reprod. Biol. Endocrinol., 19.","DOI":"10.1186\/s12958-021-00702-7"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"8815","DOI":"10.1002\/jcp.27541","article-title":"Effects of intracerebroventricular administration of irisin on the hypothalamus-pituitary-gonadal axis in male rats","volume":"234","author":"Tekin","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1055\/s-0043-115227","article-title":"Irisin and Testosterone in Men with Metabolic Syndrome","volume":"49","author":"Kamenov","year":"2017","journal-title":"Horm. Metab. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s40618-015-0403-7","article-title":"Free androgen index and Irisin in polycystic ovary syndrome","volume":"39","author":"Li","year":"2016","journal-title":"J. Endocrinol. Invest."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1210\/jc.2014-2544","article-title":"Elevated circulating levels of irisin and the effect of metformin treatment in women with polycystic ovary syndrome","volume":"100","author":"Li","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1111\/cen.13555","article-title":"Serum irisin concentrations in lean adolescents with polycystic ovary syndrome","volume":"88","author":"Bacopoulou","year":"2018","journal-title":"Clin. Endocrinol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1002\/jcp.29894","article-title":"Irisin deficiency disturbs bone metabolism","volume":"236","author":"Zhu","year":"2021","journal-title":"J. Cell Physiol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Qiao, X., Nie, Y., Ma, Y., Chen, Y., Cheng, R., Yin, W., Hu, Y., Xu, W., and Xu, L. (2016). Irisin promotes osteoblast proliferation and differentiation via activating the MAP kinase signaling pathways. Sci. Rep., 6.","DOI":"10.1038\/srep18732"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1016\/j.cell.2018.10.025","article-title":"Irisin Mediates Effects on Bone and Fat via \u03b1V Integrin Receptors","volume":"175","author":"Kim","year":"2018","journal-title":"Cell"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"12157","DOI":"10.1073\/pnas.1516622112","article-title":"The myokine irisin increases cortical bone mass","volume":"112","author":"Colaianni","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Colaianni, G., Mongelli, T., Cuscito, C., Pignataro, P., Lippo, L., Spiro, G., Notarnicola, A., Severi, I., Passeri, G., and Mori, G. (2017). Irisin prevents and restores bone loss and muscle atrophy in hind-limb suspended mice. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-02557-8"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"902186","DOI":"10.1155\/2014\/902186","article-title":"Irisin enhances osteoblast differentiation in vitro","volume":"2014","author":"Colaianni","year":"2014","journal-title":"Int. J. Endocrinol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Colucci, S.C., Buccoliero, C., Sanesi, L., Errede, M., Colaianni, G., Annese, T., Khan, M.P., Zerlotin, R., Dicarlo, M., and Schipani, E. (2021). Systemic Administration of Recombinant Irisin Accelerates Fracture Healing in Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910863"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1042\/BST20200978","article-title":"The effect of Irisin on bone cells in vivo and in vitro","volume":"49","author":"Buccoliero","year":"2021","journal-title":"Biochem. Soc. Trans."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1080\/13697137.2020.1745768","article-title":"Irisin ameliorates bone loss in ovariectomized mice","volume":"23","author":"Luo","year":"2020","journal-title":"Climacteric"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"58172","DOI":"10.7554\/eLife.58172","article-title":"Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo","volume":"9","author":"Estell","year":"2020","journal-title":"eLife"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1002\/jcp.25001","article-title":"Determinants of Muscle and Bone Aging","volume":"230","author":"Curtis","year":"2015","journal-title":"J. Cell Physiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/jcsm.12567","article-title":"Osteosarcopenia: Epidemiology, diagnosis, and treatment-facts and numbers","volume":"11","author":"Kirk","year":"2020","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"16069","DOI":"10.1038\/nrdp.2016.69","article-title":"Postmenopausal osteoporosis","volume":"2","author":"Eastell","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Zhao, R., Chen, Y., Wang, D., Zhang, C., Song, H., and Ni, G. (2023). Role of irisin in bone diseases. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1212892"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/s41390-019-0278-y","article-title":"Irisin serum levels are positively correlated with bone mineral status in a population of healthy children","volume":"85","author":"Colaianni","year":"2019","journal-title":"Pediatr. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1007\/s00198-014-2673-x","article-title":"Circulating irisin is associated with osteoporotic fractures in postmenopausal women with low bone mass but is not affected by either teriparatide or denosumab treatment for 3 months","volume":"25","author":"Anastasilakis","year":"2014","journal-title":"Osteoporos. Int."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1159\/000487689","article-title":"Lower Serum Irisin Levels Are Associated with Increased Vascular Calcification in Hemodialysis Patients","volume":"43","author":"He","year":"2018","journal-title":"Kidney Blood Press. Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.1210\/jc.2018-02216","article-title":"A Novel Interplay Between Irisin and PTH: From Basic Studies to Clinical Evidence in Hyperparathyroidism","volume":"104","author":"Palermo","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Albrecht, E., Norheim, F., Thiede, B., Holen, T., Ohashi, T., Schering, L., Lee, S., Brenmoehl, J., Thomas, S., and Drevon, C.A. (2015). Irisin\u2014A myth rather than an exercise-inducible myokine. Sci. Rep., 5.","DOI":"10.1038\/srep08889"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/14\/5098\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:11:43Z","timestamp":1760033503000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/14\/5098"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,17]]},"references-count":111,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["jcm14145098"],"URL":"https:\/\/doi.org\/10.3390\/jcm14145098","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,17]]}}}