{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:13:26Z","timestamp":1793121206115,"version":"4.5.0"},"reference-count":86,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1038\/s41390-025-03976-4","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T11:21:06Z","timestamp":1747048866000},"page":"68-76","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Circulating adipokines in girls with central precocious puberty: A systematic review and meta-analysis"],"prefix":"10.1038","volume":"99","author":[{"given":"Mei","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"3976_CR1","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/S2213-8587(15)00380-0","volume":"4","author":"AC Latronico","year":"2016","unstructured":"Latronico, A. C., Brito, V. N. & Carel, J. C. Causes, diagnosis, and treatment of central precocious puberty. Lancet Diabetes Endocrinol 4, 265\u2013274 (2016).","journal-title":"Lancet Diabetes Endocrinol"},{"key":"3976_CR2","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1007\/s40272-015-0130-8","volume":"17","author":"M Chen","year":"2015","unstructured":"Chen, M. & Eugster, E. A. Central precocious puberty: update on diagnosis and treatment. Paediatr Drugs 17, 273\u2013281 (2015).","journal-title":"Paediatr Drugs"},{"key":"3976_CR3","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1590\/2359-3997000000144","volume":"60","author":"VN Brito","year":"2016","unstructured":"Brito, V. N. et al. Central precocious puberty: revisiting the diagnosis and therapeutic management. Arch Endocrinol Metab 60, 163\u2013172 (2016).","journal-title":"Arch Endocrinol Metab"},{"key":"3976_CR4","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.jpeds.2018.12.022","volume":"208","author":"YJ Kim","year":"2019","unstructured":"Kim, Y. J. et al. Incidence and prevalence of central precocious puberty in Korea: an epidemiologic study based on a national database. J Pediatr 208, 221\u2013228 (2019).","journal-title":"J Pediatr"},{"key":"3976_CR5","doi-asserted-by":"publisher","first-page":"e2015665","DOI":"10.1001\/jamanetworkopen.2020.15665","volume":"3","author":"EV Br\u00e4uner","year":"2020","unstructured":"Br\u00e4uner, E. V. et al. Trends in the incidence of central precocious puberty and normal variant puberty among children in Denmark, 1998 to 2017. JAMA Netw Open 3, e2015665 (2020).","journal-title":"JAMA Netw Open"},{"key":"3976_CR6","doi-asserted-by":"publisher","first-page":"e195881","DOI":"10.1001\/jamapediatrics.2019.5881","volume":"174","author":"C Eckert-Lind","year":"2020","unstructured":"Eckert-Lind, C. et al. Worldwide secular trends in age at pubertal onset assessed by breast development among girls: A systematic review and meta-analysis. JAMA Pediatr 174, e195881 (2020).","journal-title":"JAMA Pediatr"},{"key":"3976_CR7","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.jpeds.2020.05.013","volume":"224","author":"H Li","year":"2020","unstructured":"Li, H. et al. Changes in children\u2019s healthcare visits during coronavirus disease-2019 pandemic in Hangzhou, China. J Pediatr 224, 146\u2013149 (2020).","journal-title":"J Pediatr"},{"key":"3976_CR8","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s13052-020-00931-3","volume":"46","author":"S Stagi","year":"2020","unstructured":"Stagi, S. et al. Increased incidence of precocious and accelerated puberty in females during and after the Italian lockdown for the coronavirus 2019 (COVID-19) pandemic. Ital J Pediatr 46, 165 (2020).","journal-title":"Ital J Pediatr"},{"key":"3976_CR9","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1210\/jc.2010-2745","volume":"96","author":"SS Mogensen","year":"2011","unstructured":"Mogensen, S. S. et al. Diagnostic work-up of 449 consecutive girls who were referred to be evaluated for precocious puberty. J Clin Endocrinol Metab 96, 1393\u20131401 (2011).","journal-title":"J Clin Endocrinol Metab"},{"key":"3976_CR10","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1210\/er.2002-0019","volume":"24","author":"AS Parent","year":"2003","unstructured":"Parent, A. S. et al. The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. Endocr Rev 24, 668\u2013693 (2003).","journal-title":"Endocr Rev"},{"key":"3976_CR11","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1080\/09513590400021060","volume":"20","author":"F Massart","year":"2005","unstructured":"Massart, F. et al. High incidence of central precocious puberty in a bounded geographic area of northwest Tuscany: an estrogen disrupter epidemic? Gynecol Endocrinol 20, 92\u201398 (2005).","journal-title":"Gynecol Endocrinol"},{"key":"3976_CR12","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1530\/EJE-07-0061","volume":"157","author":"X Luan","year":"2007","unstructured":"Luan, X. et al. Association study of the polymorphisms in the KISS1 gene with central precocious puberty in Chinese girls. Eur J Endocrinol 157, 113\u2013118 (2007).","journal-title":"Eur J Endocrinol"},{"key":"3976_CR13","doi-asserted-by":"publisher","first-page":"e8450","DOI":"10.1371\/journal.pone.0008450","volume":"4","author":"L Aksglaede","year":"2009","unstructured":"Aksglaede, L., Juul, A., Olsen, L. W. & S\u00f8rensen, T. I. Age at puberty and the emerging obesity epidemic. PLoS ONE 4, e8450 (2009).","journal-title":"PLoS ONE"},{"key":"3976_CR14","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1111\/j.2047-6310.2013.00176.x","volume":"9","author":"C De Leonibus","year":"2014","unstructured":"De Leonibus, C. et al. Timing of puberty and physical growth in obese children: a longitudinal study in boys and girls. Pediatr Obes 9, 292\u2013299 (2014).","journal-title":"Pediatr Obes"},{"key":"3976_CR15","doi-asserted-by":"publisher","first-page":"e71","DOI":"10.1111\/j.1651-2227.2011.02444.x","volume":"101","author":"Z Atay","year":"2012","unstructured":"Atay, Z. et al. The prevalence and risk factors of premature thelarche and pubarche in 4- to 8-year-old girls. Acta Paediatr 101, e71\u2013e75 (2012).","journal-title":"Acta Paediatr"},{"key":"3976_CR16","doi-asserted-by":"publisher","first-page":"4953","DOI":"10.1210\/jc.2009-1789","volume":"94","author":"R Lakshman","year":"2009","unstructured":"Lakshman, R. et al. Early age at menarche associated with cardiovascular disease and mortality. J Clin Endocrinol Metab 94, 4953\u20134960 (2009).","journal-title":"J Clin Endocrinol Metab"},{"key":"3976_CR17","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1093\/ije\/dyn251","volume":"38","author":"BK Jacobsen","year":"2009","unstructured":"Jacobsen, B. K., Oda, K., Knutsen, S. F. & Fraser, G. E. Age at menarche, total mortality and mortality from ischaemic heart disease and stroke: the Adventist Health Study, 1976-88. Int J Epidemiol 38, 245\u2013252 (2009).","journal-title":"Int J Epidemiol"},{"key":"3976_CR18","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1093\/ajcn\/43.6.879","volume":"43","author":"SM Garn","year":"1986","unstructured":"Garn, S. M., LaVelle, M., Rosenberg, K. R. & Hawthorne, V. M. Maturational timing as a factor in female fatness and obesity. Am J Clin Nutr 43, 879\u2013883 (1986).","journal-title":"Am J Clin Nutr"},{"key":"3976_CR19","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/1471-2431-3-3","volume":"3","author":"DS Freedman","year":"2003","unstructured":"Freedman, D. S. et al. The relation of menarcheal age to obesity in childhood and adulthood: the Bogalusa heart study. BMC Pediatr 3, 3 (2003).","journal-title":"BMC Pediatr"},{"key":"3976_CR20","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1093\/ajcn\/64.1.18","volume":"64","author":"FJ van Lenthe","year":"1996","unstructured":"van Lenthe, F. J., Kemper, C. G. & van Mechelen, W. Rapid maturation in adolescence results in greater obesity in adulthood: the Amsterdam Growth and Health Study. Am J Clin Nutr 64, 18\u201324 (1996).","journal-title":"Am J Clin Nutr"},{"key":"3976_CR21","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1007\/s00125-008-0948-5","volume":"51","author":"R Lakshman","year":"2008","unstructured":"Lakshman, R. et al. Association between age at menarche and risk of diabetes in adults: results from the EPIC-Norfolk cohort study. Diabetologia 51, 781\u2013786 (2008).","journal-title":"Diabetologia"},{"key":"3976_CR22","doi-asserted-by":"publisher","first-page":"1876","DOI":"10.1093\/ajcn\/87.6.1876","volume":"87","author":"M Kivim\u00e4ki","year":"2008","unstructured":"Kivim\u00e4ki, M. et al. Association of age at menarche with cardiovascular risk factors, vascular structure, and function in adulthood: the Cardiovascular Risk in Young Finns study. Am J Clin Nutr. 87, 1876\u20131882 (2008).","journal-title":"Am J Clin Nutr"},{"key":"3976_CR23","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1038\/sj.ijo.0802422","volume":"27","author":"MG Frontini","year":"2003","unstructured":"Frontini, M. G., Srinivasan, S. R. & Berenson, G. S. Longitudinal changes in risk variables underlying metabolic Syndrome X from childhood to young adulthood in female subjects with a history of early menarche: the Bogalusa Heart Study. Int J Obes Relat Metab Disord 27, 1398\u20131404 (2003).","journal-title":"Int J Obes Relat Metab Disord"},{"key":"3976_CR24","doi-asserted-by":"publisher","first-page":"2718","DOI":"10.1210\/jc.2004-1991","volume":"90","author":"KE Remsberg","year":"2005","unstructured":"Remsberg, K. E. et al. Early menarche and the development of cardiovascular disease risk factors in adolescent girls: the Fels Longitudinal Study. J Clin Endocrinol Metab 90, 2718\u20132724 (2005).","journal-title":"J Clin Endocrinol Metab"},{"key":"3976_CR25","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1067\/mpd.2001.112658","volume":"138","author":"J Steinberger","year":"2001","unstructured":"Steinberger, J. et al. Adiposity in childhood predicts obesity and insulin resistance in young adulthood. J Pediatr 138, 469\u2013473 (2001).","journal-title":"J Pediatr"},{"key":"3976_CR26","doi-asserted-by":"publisher","first-page":"204","DOI":"10.2337\/diabetes.51.1.204","volume":"51","author":"SR Srinivasan","year":"2002","unstructured":"Srinivasan, S. R., Myers, L. & Berenson, G. S. Predictability of childhood adiposity and insulin for developing insulin resistance syndrome (syndrome X) in young adulthood: the Bogalusa Heart Study. Diabetes 51, 204\u2013209 (2002).","journal-title":"Diabetes"},{"key":"3976_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mehy.2016.08.003","volume":"95","author":"F Wahab","year":"2016","unstructured":"Wahab, F., Shahab, M. & Behr, R. Hypothesis: Irisin is a metabolic trigger for the activation of the neurohormonal axis governing puberty onset. Med Hypotheses 95, 1\u20134 (2016).","journal-title":"Med Hypotheses"},{"key":"3976_CR28","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1097\/00041433-200202000-00008","volume":"13","author":"PJ Havel","year":"2002","unstructured":"Havel, P. J. Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin. Curr Opin Lipidol 13, 51\u201359 (2002).","journal-title":"Curr Opin Lipidol"},{"key":"3976_CR29","doi-asserted-by":"crossref","unstructured":"Hales, C. et al. Obesity, leptin and host defence of Streptococcus pneumoniae: the case for more human research. Eur Respir Rev 31, 220055 (2022).","DOI":"10.1183\/16000617.0055-2022"},{"key":"3976_CR30","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1002\/j.2040-4603.2018.tb00036.x","volume":"8","author":"H Fang","year":"2018","unstructured":"Fang, H. & Judd, R. L. Adiponectin regulation and function. Compr Physiol 8, 1031\u20131063 (2018).","journal-title":"Compr Physiol"},{"key":"3976_CR31","doi-asserted-by":"publisher","first-page":"4899","DOI":"10.1210\/jc.2013-2373","volume":"98","author":"KH Park","year":"2013","unstructured":"Park, K. H. et al. Circulating irisin in relation to insulin resistance and the metabolic syndrome. J Clin Endocrinol Metab 98, 4899\u20134907 (2013).","journal-title":"J Clin Endocrinol Metab"},{"key":"3976_CR32","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.2147\/DMSO.S222066","volume":"12","author":"T Chen","year":"2019","unstructured":"Chen, T. et al. Serum CTRP3 levels in obese children: a potential protective adipokine of obesity, insulin sensitivity and pancreatic \u03b2 cell function. Diabetes Metab Syndr Obes 12, 1923\u20131930 (2019).","journal-title":"Diabetes Metab Syndr Obes"},{"key":"3976_CR33","doi-asserted-by":"publisher","first-page":"e247","DOI":"10.1210\/clinem\/dgaa720","volume":"106","author":"E Kutlu","year":"2021","unstructured":"Kutlu, E. et al. Serum irisin levels in central precocious puberty and its variants. J Clin Endocrinol Metab 106, e247\u2013e254 (2021).","journal-title":"J Clin Endocrinol Metab"},{"key":"3976_CR34","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1080\/09513590.2017.1423467","volume":"34","author":"MJ Kang","year":"2018","unstructured":"Kang, M. J. et al. The usefulness of circulating levels of leptin, kisspeptin, and neurokinin B in obese girls with precocious puberty. Gynecol Endocrinol 34, 627\u2013630 (2018).","journal-title":"Gynecol Endocrinol"},{"key":"3976_CR35","doi-asserted-by":"publisher","first-page":"e1000097","DOI":"10.1371\/journal.pmed.1000097","volume":"6","author":"D Moher","year":"2009","unstructured":"Moher, D., Liberati, A., Tetzlaff, J. & Altman, D. G. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 6, e1000097 (2009).","journal-title":"PLoS Med"},{"key":"3976_CR36","first-page":"411","volume":"48","author":"L Chatenoud","year":"2000","unstructured":"Chatenoud, L. & Vecchia, C. Comments: Meta-analysis of observational studies in epidemiology. Revue d \u00c9pid\u00e9miologie et de Sant\u00e9 Publique 48, 411\u2013412 (2000).","journal-title":"Revue d \u00c9pid\u00e9miologie et de Sant\u00e9 Publique"},{"key":"3976_CR37","doi-asserted-by":"crossref","unstructured":"Zhou, X. et al. Systematic review and meta-analysis on the effects of astaxanthin on human skin ageing. Nutrients 13, 2917 (2021).","DOI":"10.3390\/nu13092917"},{"key":"3976_CR38","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1186\/s13287-021-02533-0","volume":"12","author":"R Wang","year":"2021","unstructured":"Wang, R. et al. Stem cell therapy for Crohn\u2019s disease: systematic review and meta-analysis of preclinical and clinical studies. Stem Cell Res Ther 12, 463 (2021).","journal-title":"Stem Cell Res Ther"},{"key":"3976_CR39","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/s10654-010-9491-z","volume":"25","author":"A Stang","year":"2010","unstructured":"Stang, A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25, 603\u2013605 (2010).","journal-title":"Eur J Epidemiol"},{"key":"3976_CR40","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1002\/(SICI)1097-0258(19980430)17:8<841::AID-SIM781>3.0.CO;2-D","volume":"17","author":"RJ Hardy","year":"1998","unstructured":"Hardy, R. J. & Thompson, S. G. Detecting and describing heterogeneity in meta\u2010analysis. Stat Med. 17, 841\u2013856 (1998).","journal-title":"Stat Med"},{"key":"3976_CR41","doi-asserted-by":"publisher","first-page":"102578","DOI":"10.1016\/j.ctim.2020.102578","volume":"54","author":"M Huang","year":"2020","unstructured":"Huang, M. et al. The effect of gum consumption on anthropometric characteristics and cardiac disorders: A systematic review and meta-analysis of randomized controlled trials. Complement Ther Med. 54, 102578 (2020).","journal-title":"Complement Ther Med"},{"key":"3976_CR42","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","volume":"7","author":"R DerSimonian","year":"1986","unstructured":"DerSimonian, R. & Laird, N. Meta-analysis in clinical trials. Control Clin Trials 7, 177\u2013188 (1986).","journal-title":"Control Clin Trials"},{"key":"3976_CR43","first-page":"CR206","volume":"8","author":"KA Larmore","year":"2002","unstructured":"Larmore, K. A. et al. Leptin and estradiol as related to change in pubertal status and body weight. Med Sci Mon 8, CR206\u2013CR210 (2002).","journal-title":"Med Sci Mon"},{"key":"3976_CR44","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1515\/JPEM.2008.21.3.213","volume":"21","author":"PH Su","year":"2008","unstructured":"Su, P. H. et al. A study of anthropomorphic and biochemical characteristics in girls with central precocious puberty and thelarche variant. J Pediatr Endocrinol Metabol 21, 213\u2013220 (2008).","journal-title":"J Pediatr Endocrinol Metabol"},{"key":"3976_CR45","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1016\/j.peptides.2011.07.016","volume":"32","author":"J Pita","year":"2011","unstructured":"Pita, J. et al. Circulating kisspeptin levels exhibit sexual dimorphism in adults, are increased in obese prepubertal girls and do not suffer modifications in girls with idiopathic central precocious puberty. Peptides 32, 1781\u20131786 (2011).","journal-title":"Peptides"},{"key":"3976_CR46","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/pr.2011.69","volume":"71","author":"PH Su","year":"2012","unstructured":"Su, P. H. et al. Study of leptin levels and gene polymorphisms in patients with central precocious puberty. Pediatr Res. 71, 361\u2013367 (2012).","journal-title":"Pediatr Res"},{"key":"3976_CR47","first-page":"419","volume":"86","author":"MJ Kang","year":"2016","unstructured":"Kang, M. J. et al. The influences of circulating leptin, kisspeptin, and neurokinin B levels to precocious puberty in obese girls. Hormone Res Paediatr 86, 419\u2013419 (2016).","journal-title":"Hormone Res Paediatr"},{"key":"3976_CR48","doi-asserted-by":"publisher","first-page":"2506","DOI":"10.1071\/RD16282_CO","volume":"29","author":"C Sitticharoon","year":"2017","unstructured":"Sitticharoon, C. et al. Corrigendum to: Increased high molecular weight adiponectin, but decreased total adiponectin and kisspeptin, in central precocious puberty compared with aged-matched prepubertal girls. Reprod Fertil, Dev 29, 2506 (2017).","journal-title":"Reprod Fertil, Dev"},{"key":"3976_CR49","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2021.155660","volume":"148","author":"JN Zurita-Cruz","year":"2021","unstructured":"Zurita-Cruz, J. N. et al. Altered cardiometabolic profile in girls with central precocious puberty and adipokines: A propensity score matching analysis. Cytokine 148, 155660 (2021).","journal-title":"Cytokine"},{"key":"3976_CR50","doi-asserted-by":"crossref","unstructured":"Chen, Y. et al. Serum irisin levels increase in girls with central precocious puberty not dependent on BMI: a pilot study. Endocrine Connect 11, e220028 (2022).","DOI":"10.1530\/EC-22-0028"},{"key":"3976_CR51","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/7928344","volume":"2022","author":"Z He","year":"2022","unstructured":"He, Z. & Yuan, B. Diagnostic value of combined detection of pelvic ultrasound and serum LH, FSH, and E2 Levels in children with idiopathic central precocious puberty. Evid Based Complement Alternat Med. 2022, 7928344 (2022).","journal-title":"Evid Based Complement Alternat Med"},{"key":"3976_CR52","doi-asserted-by":"publisher","first-page":"e26076","DOI":"10.1371\/journal.pone.0026076","volume":"6","author":"D St\u00f6ckl","year":"2011","unstructured":"St\u00f6ckl, D. et al. Age at menarche and its association with the metabolic syndrome and its components: results from the KORA F4 study. PLoS ONE 6, e26076 (2011).","journal-title":"PLoS ONE"},{"key":"3976_CR53","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1159\/000242441","volume":"54","author":"I Labayen","year":"2009","unstructured":"Labayen, I. et al. The effect of early menarche on later body composition and fat distribution in female adolescents: role of birth weight. Ann Nutr Metab 54, 313\u2013320 (2009).","journal-title":"Ann Nutr Metab"},{"key":"3976_CR54","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/1471-2431-14-72","volume":"14","author":"J Benedet","year":"2014","unstructured":"Benedet, J. et al. Association of sexual maturation with excess body weight and height in children and adolescents. BMC Pediatr 14, 72 (2014).","journal-title":"BMC Pediatr"},{"key":"3976_CR55","doi-asserted-by":"publisher","first-page":"3224","DOI":"10.1210\/jc.2013-3902","volume":"99","author":"J Pinkney","year":"2014","unstructured":"Pinkney, J. et al. Adiposity, chronic inflammation, and the prepubertal decline of sex hormone binding globulin in children: evidence for associations with the timing of puberty (Earlybird 58). J Clin Endocrinol Metab 99, 3224\u20133232 (2014).","journal-title":"J Clin Endocrinol Metab"},{"key":"3976_CR56","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1210\/jc.2014-3748","volume":"100","author":"L Lazar","year":"2015","unstructured":"Lazar, L. et al. Treated and untreated women with idiopathic precocious puberty: BMI evolution, metabolic outcome, and general health between third and fifth decades. J Clin Endocrinol Metab 100, 1445\u20131451 (2015).","journal-title":"J Clin Endocrinol Metab"},{"key":"3976_CR57","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1038\/oby.2005.260","volume":"13","author":"JG Woo","year":"2005","unstructured":"Woo, J. G. et al. Adolescent sex differences in adiponectin are conditional on pubertal development and adiposity. Obes Res. 13, 2095\u20132101 (2005).","journal-title":"Obes Res"},{"key":"3976_CR58","doi-asserted-by":"publisher","first-page":"53","DOI":"10.33549\/physiolres.930280","volume":"52","author":"R Pilcov\u00e1","year":"2003","unstructured":"Pilcov\u00e1, R. et al. Leptin levels in obese children: effects of gender, weight reduction and androgens. Physiol Res. 52, 53\u201360 (2003).","journal-title":"Physiol Res"},{"key":"3976_CR59","doi-asserted-by":"publisher","first-page":"233","DOI":"10.4274\/jcrpe.v1i5.233","volume":"1","author":"A Alika\u015fifo\u011flu","year":"2009","unstructured":"Alika\u015fifo\u011flu, A. et al. The relationship between serum adiponectin, tumor necrosis factor-alpha, leptin levels and insulin sensitivity in childhood and adolescent obesity: adiponectin is a marker of metabolic syndrome. J Clin Res Pediatr Endocrinol 1, 233\u2013239 (2009).","journal-title":"J Clin Res Pediatr Endocrinol"},{"key":"3976_CR60","doi-asserted-by":"crossref","unstructured":"Vilari\u00f1o-Garc\u00eda, T. et al. Role of leptin in obesity, cardiovascular disease, and type 2 diabetes. Int J Mol Sci. 25, 2338 (2024).","DOI":"10.3390\/ijms25042338"},{"key":"3976_CR61","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1095\/biolreprod60.2.216","volume":"60","author":"MJ Cunningham","year":"1999","unstructured":"Cunningham, M. J., Clifton, D. K. & Steiner, R. A. Leptin\u2019s actions on the reproductive axis: perspectives and mechanisms. Biol Reprod 60, 216\u2013222 (1999).","journal-title":"Biol Reprod"},{"key":"3976_CR62","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.yfrne.2010.06.002","volume":"31","author":"TA Dardeno","year":"2010","unstructured":"Dardeno, T. A. et al. Leptin in human physiology and therapeutics. Front Neuroendocrinol 31, 377\u2013393 (2010).","journal-title":"Front Neuroendocrinol"},{"key":"3976_CR63","doi-asserted-by":"publisher","first-page":"T49","DOI":"10.1530\/JOE-14-0245","volume":"223","author":"SH Chou","year":"2014","unstructured":"Chou, S. H. & Mantzoros, C. 20 years of leptin: role of leptin in human reproductive disorders. J Endocrinol 223, T49\u2013T62 (2014).","journal-title":"J Endocrinol"},{"key":"3976_CR64","first-page":"2260","volume":"83","author":"MR Palmert","year":"1998","unstructured":"Palmert, M. R., Radovick, S. & Boepple, P. A. Leptin levels in children with central precocious puberty. J Clin Endocrinol Metab 83, 2260\u20132265 (1998).","journal-title":"J Clin Endocrinol Metab"},{"key":"3976_CR65","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.peptides.2014.12.011","volume":"64","author":"A Abac\u0131","year":"2015","unstructured":"Abac\u0131, A. et al. Significance of serum neurokinin B and kisspeptin levels in the differential diagnosis of premature thelarche and idiopathic central precocious puberty. Peptides 64, 29\u201333 (2015).","journal-title":"Peptides"},{"key":"3976_CR66","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1111\/j.1463-1326.2008.00852.x","volume":"10","author":"Anubhuti","year":"2008","unstructured":"Anubhuti & Arora, S. Leptin and its metabolic interactions: an update. Diabetes Obes Metab 10, 973\u2013993 (2008).","journal-title":"Diabetes Obes Metab"},{"key":"3976_CR67","doi-asserted-by":"publisher","first-page":"T63","DOI":"10.1530\/JOE-14-0480","volume":"223","author":"IS Farooqi","year":"2014","unstructured":"Farooqi, I. S. O\u2019Rahilly, S., 20 years of leptin: human disorders of leptin action. J Endocrinol 223, T63\u2013T70 (2014).","journal-title":"J Endocrinol"},{"key":"3976_CR68","doi-asserted-by":"publisher","first-page":"519","DOI":"10.4158\/EP161620.OR","volume":"23","author":"JN Zurita-Cruz","year":"2017","unstructured":"Zurita-Cruz, J. N. et al. Relationship Between Serum Leptin Levels And Weight Gain In Girls With Central Precocious Puberty At 1-Year Follow-Up. Endocr Pract 23, 519\u2013525 (2017).","journal-title":"Endocr Pract"},{"key":"3976_CR69","doi-asserted-by":"publisher","first-page":"4053","DOI":"10.1210\/jc.2004-0303","volume":"89","author":"A B\u00f6ttner","year":"2004","unstructured":"B\u00f6ttner, A. et al. Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metab 89, 4053\u20134061 (2004).","journal-title":"J Clin Endocrinol Metab"},{"key":"3976_CR70","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.peptides.2014.09.014","volume":"61","author":"S Aydin","year":"2014","unstructured":"Aydin, S. et al. A comprehensive immunohistochemical examination of the distribution of the fat-burning protein irisin in biological tissues. Peptides 61, 130\u2013136 (2014).","journal-title":"Peptides"},{"key":"3976_CR71","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.peptides.2019.01.004","volume":"113","author":"Q Ruan","year":"2019","unstructured":"Ruan, Q. et al. The effects of both age and sex on irisin levels in paired plasma and cerebrospinal fluid in healthy humans. Peptides 113, 41\u201351 (2019).","journal-title":"Peptides"},{"key":"3976_CR72","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/2628968","volume":"2017","author":"L Elizondo-Montemayor","year":"2017","unstructured":"Elizondo-Montemayor, L. et al. Association of irisin plasma levels with anthropometric parameters in children with underweight, normal weight, overweight, and obesity. Biomed Res Int. 2017, 2628968 (2017).","journal-title":"Biomed Res Int"},{"key":"3976_CR73","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.metabol.2017.05.007","volume":"73","author":"HB Jang","year":"2017","unstructured":"Jang, H. B. et al. Association of circulating irisin levels with metabolic and metabolite profiles of Korean adolescents. Metabolism 73, 100\u2013108 (2017).","journal-title":"Metabolism"},{"key":"3976_CR74","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.cyto.2016.12.018","volume":"94","author":"E Nigro","year":"2017","unstructured":"Nigro, E. et al. Adiponectin profile and Irisin expression in Italian obese children: Association with insulin-resistance. Cytokine 94, 8\u201313 (2017).","journal-title":"Cytokine"},{"key":"3976_CR75","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1210\/jc.2015-1208","volume":"100","author":"T Reinehr","year":"2015","unstructured":"Reinehr, T., Elfers, C., Lass, N. & Roth, C. L. Irisin and its relation to insulin resistance and puberty in obese children: a longitudinal analysis. J Clin Endocrinol Metab 100, 2123\u20132130 (2015).","journal-title":"J Clin Endocrinol Metab"},{"key":"3976_CR76","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1530\/JOE-18-0574","volume":"241","author":"F Wahab","year":"2019","unstructured":"Wahab, F. et al. Irisin in the primate hypothalamus and its effect on GnRH in vitro. J Endocrinol 241, 175\u2013187 (2019).","journal-title":"J Endocrinol"},{"key":"3976_CR77","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1530\/REP-20-0072","volume":"160","author":"N Ulker","year":"2020","unstructured":"Ulker, N. et al. Irisin may have a role in pubertal development and regulation of reproductive function in rats. Reproduction 160, 281\u2013292 (2020).","journal-title":"Reproduction"},{"key":"3976_CR78","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.repbio.2017.05.011","volume":"17","author":"L Poretsky","year":"2017","unstructured":"Poretsky, L. et al. Reproductive effects of irisin: Initial in vitro studies. Reprod Biol 17, 285\u2013288 (2017).","journal-title":"Reprod Biol"},{"key":"3976_CR79","doi-asserted-by":"publisher","first-page":"591","DOI":"10.6061\/clinics\/2012(06)08","volume":"67","author":"SB Alessandri","year":"2012","unstructured":"Alessandri, S. B. et al. Bone mineral density and body composition in girls with idiopathic central precocious puberty before and after treatment with a gonadotropin-releasing hormone agonist. Clinics 67, 591\u2013596 (2012).","journal-title":"Clinics"},{"key":"3976_CR80","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1159\/000197862","volume":"89","author":"E Chiocca","year":"2009","unstructured":"Chiocca, E. et al. Body mass index and body composition in adolescents treated with gonadotropin-releasing hormone analogue triptorelin depot for central precocious puberty: data at near final height. Neuroendocrinology 89, 441\u2013447 (2009).","journal-title":"Neuroendocrinology"},{"key":"3976_CR81","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1159\/000479369","volume":"89","author":"F de Zegher","year":"2018","unstructured":"de Zegher, F., Garc\u00eda Beltr\u00e1n, C., L\u00f3pez-Bermejo, A. & Ib\u00e1\u00f1ez, L. Metformin for Rapidly Maturing Girls with Central Adiposity: Less Liver Fat and Slower Bone Maturation. Horm Res Paediatr 89, 136\u2013140 (2018).","journal-title":"Horm Res Paediatr"},{"key":"3976_CR82","doi-asserted-by":"publisher","first-page":"e0226303","DOI":"10.1371\/journal.pone.0226303","volume":"14","author":"J Bassols","year":"2019","unstructured":"Bassols, J. et al. Effects of metformin administration on endocrine-metabolic parameters, visceral adiposity and cardiovascular risk factors in children with obesity and risk markers for metabolic syndrome: A pilot study. PLoS ONE 14, e0226303 (2019).","journal-title":"PLoS ONE"},{"key":"3976_CR83","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1016\/S0015-0282(02)04925-7","volume":"79","author":"R Mansfield","year":"2003","unstructured":"Mansfield, R. et al. Metformin has direct effects on human ovarian steroidogenesis. Fertil Steril 79, 956\u2013962 (2003).","journal-title":"Fertil Steril"},{"key":"3976_CR84","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1095\/biolreprod.106.055749","volume":"76","author":"L Tosca","year":"2007","unstructured":"Tosca, L., Chabrolle, C., Uzbekova, S. & Dupont, J. Effects of metformin on bovine granulosa cells steroidogenesis: possible involvement of adenosine 5\u2019 monophosphate-activated protein kinase (AMPK). Biol Reprod 76, 368\u2013378 (2007).","journal-title":"Biol Reprod"},{"key":"3976_CR85","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/S0026-0495(97)90066-4","volume":"46","author":"EM Velazquez","year":"1997","unstructured":"Velazquez, E. M., Mendoza, S. G., Wang, P. & Glueck, C. J. Metformin therapy is associated with a decrease in plasma plasminogen activator inhibitor-1, lipoprotein(a), and immunoreactive insulin levels in patients with the polycystic ovary syndrome. Metabolism 46, 454\u2013457 (1997).","journal-title":"Metabolism"},{"key":"3976_CR86","first-page":"319","volume":"125","author":"CJ Glueck","year":"1995","unstructured":"Glueck, C. J. et al. Hypofibrinolytic and atherogenic risk factors for stroke. J Lab Clin Med. 125, 319\u2013325 (1995).","journal-title":"J Lab Clin Med"}],"container-title":["Pediatric Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-03976-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-03976-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-03976-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T23:06:45Z","timestamp":1771542405000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-03976-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,12]]},"references-count":86,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["3976"],"URL":"https:\/\/doi.org\/10.1038\/s41390-025-03976-4","relation":{},"ISSN":["0031-3998","1530-0447"],"issn-type":[{"value":"0031-3998","type":"print"},{"value":"1530-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,12]]},"assertion":[{"value":"6 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The research type of this article is systematic review and meta-analysis, thus no ethical approval is needed.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}