{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:01:47Z","timestamp":1753891307060,"version":"3.41.2"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Childhood obesity has increased worldwide, becoming a significant public health concern. Brain-derived neurotrophic factor (BDNF) plays an important role in the central regulation of food intake and body weight, but little is known regarding its role in childhood obesity. Next to obesity, BDNF has been linked to obstructive sleep apnea (OSA) and endothelial dysfunction, two obesity-related comorbidities. The aim of this study is to investigate how BDNF, OSA and endothelial dysfunction interact in children with obesity and to determine the effect of weight loss on serum BDNF levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Children and adolescents with obesity aged 8\u201318 years who were enrolled in a multidisciplinary obesity treatment (MOT) in a tertiary hospital, were prospectively included. Several examinations were conducted during this MOT; at baseline, after 6 months and after 12 months, including the assessment of endothelial function, body composition measurements and a polysomnography. BDNF levels were measured on a serum sample by means of ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 103 patients with obesity was included, of which 20 had OSA (19.4%). BDNF levels were comparable in children with obesity and OSA and children with obesity but without OSA (26.75 vs. 27.87 ng\/ml, <jats:italic>p<\/jats:italic> = 0.6). No correlations were found between BDNF and sleep-related variables or between BDNF and endothelial function parameters nor between BDNF and adiposity measures. To investigate if the interaction between OSA and endothelial dysfunction had an influence on BDNF levels, a general linear model was used. This model revealed that a diagnosis of OSA, as well as the interaction between OSA and maximal endothelial dilatation, contributed significantly (<jats:italic>p<\/jats:italic> = 0.03, <jats:italic>p<\/jats:italic> = 0.04, respectively) to BDNF levels. After 1 year of weight loss therapy, BDNF levels did not change (26.18 vs. 25.46 ng\/ml, <jats:italic>p<\/jats:italic> = 0.7) in our population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>BDNF concentrations were comparable in children with obesity, both with and without OSA, indicating that BDNF levels are not affected by OSA. However, we did find an interaction effect of OSA and endothelial function on BDNF levels.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2021.835515","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T06:12:00Z","timestamp":1642659120000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["The Role of Brain-Derived Neurotrophic Factor in Obstructive Sleep Apnea and Endothelial Function in a Pediatric Population With Obesity"],"prefix":"10.3389","volume":"8","author":[{"given":"Sanae","family":"Makhout","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eline","family":"Vermeiren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolien","family":"Van De Maele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc","family":"Bruyndonckx","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedicte Y.","family":"De Winter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim","family":"Van Hoorenbeeck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stijn L.","family":"Verhulst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annelies","family":"Van Eyck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1186\/s12916-019-1449-8","article-title":"The epidemiological burden of obesity in childhood: a worldwide epidemic requiring urgent action","volume":"17","author":"Di Cesare","year":"2019","journal-title":"BMC Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"409","DOI":"10.5664\/jcsm.26864","article-title":"Endothelial dysfunction in obstructive sleep apnea","volume":"3","author":"Budhiraja","year":"2007","journal-title":"J Clin Sleep Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1164\/rccm.200306-767OC","article-title":"Endothelial function in obstructive sleep apnea and response to treatment","volume":"169","author":"Ip","year":"2004","journal-title":"Am J Respir Crit Care Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1164\/rccm.200306-756OC","article-title":"Sleep apnea and markers of vascular endothelial function in a large community sample of older adults","volume":"169","author":"Nieto","year":"2004","journal-title":"Am J Respir Crit Care Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.prrv.2016.05.004","article-title":"Neurocognitive and behavioural outcomes following intervention for obstructive sleep apnoea syndrome in children","volume":"20","author":"Konstantinopoulou","year":"2016","journal-title":"Paediatr Respir Rev"},{"key":"B6","doi-asserted-by":"publisher","first-page":"5137947","DOI":"10.1155\/2018\/5137947","article-title":"Leptin and leptin resistance in the pathogenesis of obstructive sleep apnea: a possible link to oxidative stress and cardiovascular complications","volume":"2018","author":"Berger","year":"2018","journal-title":"Oxid Med Cell Longev"},{"key":"B7","first-page":"123","article-title":"Evidence for lipid peroxidation in obstructive sleep apnea","volume":"27","author":"Lavie","year":"2004","journal-title":"Sleep"},{"key":"B8","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1152\/physrev.00043.2008","article-title":"Pathophysiology of sleep apnea","volume":"90","author":"Dempsey","year":"2010","journal-title":"Physiol Rev"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1164\/rccm.201605-0911ED","article-title":"Obstructive sleep apnea, obesity, and endothelial dysfunction in children","volume":"194","author":"Katz","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1378\/chest.11-1777","article-title":"Endothelial dysfunction in children without hypertension: potential contributions of obesity and obstructive sleep apnea","volume":"141","author":"Bhattacharjee","year":"2012","journal-title":"Chest"},{"key":"B11","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.sleep.2021.08.002","article-title":"The impact of obstructive sleep apnea on endothelial function during weight loss in an obese pediatric population","volume":"86","author":"Jacobs","year":"2021","journal-title":"Sleep Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.5114\/aoms.2015.56342","article-title":"Brain-derived neurotrophic factor and its clinical implications","volume":"11","author":"Bathina","year":"2015","journal-title":"Arch Med Sci"},{"key":"B13","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.pnpbp.2011.08.003","article-title":"Association between brain-derived neurotrophic factor Val66Met and obesity in children and adolescents","volume":"36","author":"Skledar","year":"2012","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"B14","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.metabol.2012.08.001","article-title":"Brain-derived neurotrophic factor and its relation to leptin in obese children before and after weight loss","volume":"62","author":"Roth","year":"2013","journal-title":"Metabolism"},{"key":"B15","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1111\/j.1365-2265.2012.04431.x","article-title":"Plasma brain-derived neurotrophic factor in prepubertal obese children: results from a 2-year lifestyle intervention programme","volume":"77","author":"Corripio","year":"2012","journal-title":"Clin Endocrinol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.nbd.2010.05.020","article-title":"Brain-derived neurotrophic factor rescues and prevents chronic intermittent hypoxia-induced impairment of hippocampal long-term synaptic plasticity","volume":"40","author":"Xie","year":"2010","journal-title":"Neurobiol Dis"},{"key":"B17","doi-asserted-by":"publisher","first-page":"363","DOI":"10.3389\/fncel.2019.00363","article-title":"Brain-derived neurotrophic factor: a key molecule for memory in the healthy and the pathological brain","volume":"13","author":"Miranda","year":"2019","journal-title":"Front Cell Neurosci"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e1161","DOI":"10.1542\/peds.2010-0688","article-title":"Neurocognitive and endothelial dysfunction in children with obstructive sleep apnea","volume":"126","author":"Gozal","year":"2010","journal-title":"Pediatrics"},{"key":"B19","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1111\/apha.12743","article-title":"Brain-derived neurotrophic factor of the cerebral microvasculature: a forgotten and nitric oxide-dependent contributor of brain-derived neurotrophic factor in the brain","volume":"219","author":"Monnier","year":"2017","journal-title":"Acta Physiol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.tcm.2007.03.002","article-title":"Brain-derived neurotrophic factor: a newly described mediator of angiogenesis","volume":"17","author":"Kermani","year":"2007","journal-title":"Trends Cardiovasc Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1186\/s12889-018-5950-3","article-title":"WELCOME: improving WEight controL and CO-Morbidities in children with obesity via Executive function training: study protocol for a randomized controlled trial","volume":"18","author":"Naets","year":"2018","journal-title":"BMC Public Health"},{"key":"B22","doi-asserted-by":"publisher","first-page":"794256","DOI":"10.3389\/fped.2021.794256","article-title":"Improving treatment outcome in children with obesity by an online self-control training: a randomized controlled trial","volume":"9","author":"Vermeiren","year":"2021","journal-title":"Front Pediatr"},{"key":"B23","doi-asserted-by":"publisher","first-page":"680","DOI":"10.3109\/03014460903049074","article-title":"References for growth and pubertal development from birth to 21 years in Flanders, Belgium","volume":"36","author":"Roelants","year":"2009","journal-title":"Ann Hum Biol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1136\/bmj.320.7244.1240","article-title":"Establishing a standard definition for child overweight and obesity worldwide: international survey","volume":"320","author":"Cole","year":"2000","journal-title":"BMJ"},{"key":"B25","doi-asserted-by":"publisher","first-page":"S48","DOI":"10.1038\/ijo.2014.135","article-title":"Blood pressure reference values for European non-overweight school children: the IDEFICS study","volume":"38","author":"Barba","year":"2014","journal-title":"Int J Obes"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e20171904","DOI":"10.1542\/peds.2017-1904","article-title":"Clinical practice guideline for screening and management of high blood pressure in children and adolescents","volume":"140","author":"Flynn","year":"2017","journal-title":"Pediatrics"},{"key":"B27","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/s41430-020-00738-9","article-title":"Comparison of bioimpedance spectroscopy and dual energy X-ray absorptiometry for assessing body composition changes in obese children during weight loss","volume":"75","author":"Vermeiren","year":"2020","journal-title":"Eur J Clin Nutr"},{"key":"B28","doi-asserted-by":"publisher","first-page":"3183","DOI":"10.1016\/j.ijcard.2013.07.236","article-title":"Methodological considerations and practical recommendations for the application of peripheral arterial tonometry in children and adolescents","volume":"168","author":"Bruyndonckx","year":"2013","journal-title":"Int J Cardiol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1164\/ajrccm.153.2.8564147","article-title":"American Thoracic Society","volume":"153","year":"1996","journal-title":"Am J Respir Crit Care Med"},{"key":"B30","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1136\/adc.2006.101089","article-title":"Sleep-disordered breathing in overweight and obese children and adolescents: prevalence, characteristics and the role of fat distribution","volume":"92","author":"Verhulst","year":"2007","journal-title":"Arch Dis Child"},{"key":"B31","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.jpeds.2017.12.056","article-title":"Clinical predictors of residual sleep apnea after weight loss therapy in obese adolescents","volume":"196","author":"Van Eyck","year":"2018","journal-title":"J Pediatr"},{"key":"B32","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1183\/13993003.00385-2015","article-title":"Obstructive sleep disordered breathing in 2- to 18-year-old children: diagnosis and management","volume":"47","author":"Kaditis","year":"2016","journal-title":"Eur Respir J"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e0227834","DOI":"10.1371\/journal.pone.0227834","article-title":"Protective role of brain derived neurotrophic factor (BDNF) in obstructive sleep apnea syndrome (OSAS) patients","volume":"15","author":"Flores","year":"2020","journal-title":"PLoS ONE"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1942","DOI":"10.1177\/147323001003800607","article-title":"Changes of serum brain-derived neurotrophic factor in children with obstructive sleep apnoea-hypopnoea syndrome following adenotonsillectomy","volume":"38","author":"Wang","year":"2010","journal-title":"J Int Med Res"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neuroscience.2012.01.017","article-title":"Acute intermittent hypoxia-induced expression of brain-derived neurotrophic factor is disrupted in the brainstem of methyl-CpG-binding protein 2 null mice","volume":"206","author":"Vermehren-Schmaedick","year":"2012","journal-title":"Neuroscience"},{"key":"B36","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1159\/000047710","article-title":"Nerve growth factor and transforming growth factor-beta serum levels in acute stroke patients. Possible involvement of neurotrophins in cerebrovascular disease","volume":"12","author":"Stanzani","year":"2001","journal-title":"Cerebrovasc Dis"},{"key":"B37","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1136\/thx.2004.038208","article-title":"Regulation of brain-derived neurotrophic factor (BDNF) during sleep apnoea treatment","volume":"60","author":"Staats","year":"2005","journal-title":"Thorax"},{"key":"B38","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1016\/j.jpeds.2009.04.060","article-title":"Impaired vascular function in obese adolescents with insulin resistance","volume":"155","author":"Mahmud","year":"2009","journal-title":"J Pediatr"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1253\/circj.CJ-14-1303","article-title":"Association between endothelial function (assessed on reactive hyperemia peripheral arterial tonometry) and obstructive sleep apnea, visceral fat accumulation, and serum adiponectin","volume":"79","author":"Azuma","year":"2015","journal-title":"Circ J"},{"key":"B40","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.sleep.2018.07.023","article-title":"Polysomnographic correlates of endothelial function in children with obstructive sleep apnea","volume":"52","author":"Zhang","year":"2018","journal-title":"Sleep Med"},{"key":"B41","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1136\/heartjnl-2012-303009","article-title":"Impaired endothelial function in persons with obstructive sleep apnoea: impact of obesity","volume":"99","author":"Namtvedt","year":"2013","journal-title":"Heart"},{"key":"B42","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.pcad.2008.08.002","article-title":"Endothelial function in obstructive sleep apnea","volume":"51","author":"Atkeson","year":"2009","journal-title":"Prog Cardiovasc Dis"},{"key":"B43","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.jfma.2020.04.011","article-title":"Serum brain-derived neurotrophic factor and neurocognitive function in children with type 1 diabetes","volume":"120","author":"Chen","year":"2021","journal-title":"J Formos Med Assoc"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1589\/jpts.26.1199","article-title":"The effects of 12 weeks regular aerobic exercise on brain-derived neurotrophic factor and inflammatory factors in juvenile obesity and type 2 diabetes mellitus","volume":"26","author":"Lee","year":"2014","journal-title":"J Phys Ther Sci"},{"key":"B45","doi-asserted-by":"publisher","first-page":"4537274","DOI":"10.1155\/2019\/4537274","article-title":"Changes in circulating BDNF in relation to Sex, Diet, and exercise: a 12-week randomized controlled study in overweight and obese participants","volume":"2019","author":"Glud","year":"2019","journal-title":"J Obes"},{"key":"B46","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.neurobiolaging.2004.03.002","article-title":"The impact of age, weight and gender on BDNF levels in human platelets and plasma","volume":"26","author":"Lommatzsch","year":"2005","journal-title":"Neurobiol Aging"},{"key":"B47","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1007\/s12020-008-9090-x","article-title":"Evaluation of the effect of caloric restriction on serum BDNF in overweight and obese subjects: preliminary evidences","volume":"33","author":"Araya","year":"2008","journal-title":"Endocrine"},{"key":"B48","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3389\/neuro.24.005.2010","article-title":"The impact of dietary energy intake on cognitive aging","volume":"2","author":"Mattson","year":"2010","journal-title":"Front Aging Neurosci"},{"key":"B49","doi-asserted-by":"publisher","first-page":"111","DOI":"10.2144\/000114204","article-title":"Influence of clotting duration on brain-derived neurotrophic factor (BDNF) dosage in serum","volume":"57","author":"Maffioletti","year":"2014","journal-title":"Biotechniques"},{"key":"B50","doi-asserted-by":"publisher","first-page":"17989","DOI":"10.1038\/srep17989","article-title":"A method for reproducible measurements of serum BDNF: comparison of the performance of six commercial assays","volume":"5","author":"Polacchini","year":"2015","journal-title":"Sci Rep"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.835515\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T06:12:03Z","timestamp":1642659123000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.835515\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,20]]},"references-count":50,"alternative-id":["10.3389\/fmed.2021.835515"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2021.835515","relation":{},"ISSN":["2296-858X"],"issn-type":[{"type":"electronic","value":"2296-858X"}],"subject":[],"published":{"date-parts":[[2022,1,20]]},"article-number":"835515"}}