{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:26:47Z","timestamp":1780918007038,"version":"3.54.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Polycystic ovary syndrome (PCOS) in adolescence is characterized by hormonal imbalance, low-grade inflammation, oxidative stress, and metabolic dysfunction. Brain-derived neurotrophic factor (BDNF) regulates energy homeostasis and neuroimmune signaling and may act as a neuroimmunometabolic integrator in PCOS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Forty adolescent females with PCOS (26 normal weight and 14 with overweight and obesity) were evaluated. Serum BDNF, omega-3 fatty acids (EPA, DHA), uric acid, metabolic and hormonal indices, and total antioxidant capacity (T-AOC) were measured. Dietary intake and physical activity were assessed using validated tools.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Serum BDNF concentrations did not differ between BMI phenotypes. After FDR correction, significant dietary associations were observed only in normal-weight participants, including energy, protein, fat, and unsaturated fatty acids. No dietary associations remained significant in patients with overweight and obesity. Across both phenotypes, BDNF was positively associated with IL-1\u03b2, MDA, T-AOC, EPA, and uric acid. IL-6, TNF-\n                      <jats:italic>\u03b1<\/jats:italic>\n                      , and DHA remained significant only in normal-weight participants. No associations were found with CRP, lipid profile, sex hormones, or glucose\u2013insulin parameters.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Circulating BDNF was associated with dietary, inflammatory, and oxidative parameters, with limited evidence for endocrine associations. These findings suggest that BDNF may reflect an integrated neuroimmunometabolic profile in adolescent PCOS and should be considered exploratory, requiring confirmation in longitudinal studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1830074","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:43:45Z","timestamp":1779342225000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Serum BDNF as an integrative neuro-immunometabolic marker in adolescent polycystic ovary syndrome: divergent dietary and inflammatory associations across weight phenotypes"],"prefix":"10.3389","volume":"13","author":[{"given":"Ma\u0142gorzata","family":"Mizgier","sequence":"first","affiliation":[{"name":"Department of Sports Dietetics, Faculty of Health Sciences, Poznan University of Physical Education","place":["Poznan, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Formanowicz","sequence":"additional","affiliation":[{"name":"Chair and Department of Medical Chemistry and Laboratory Medicine, Poznan University of Medical Sciences","place":["Poznan, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Sansoni","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Biochemistry and Advanced Diagnostics, I.R.C.C.S. Ospedale Galeazzi-Sant\u2019Ambrogio","place":["Milano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gra\u017cyna","family":"Jarz\u0105bek-Bielecka","sequence":"additional","affiliation":[{"name":"Division of Gynecology, Department of Gynecology, Center of General Sexology and Sexology of Developmental Age, Poznan University of Medical Sciences","place":["Poznan, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Biochemistry and Advanced Diagnostics, I.R.C.C.S. Ospedale Galeazzi-Sant\u2019Ambrogio","place":["Milano, Italy"]},{"name":"Department of Athletics, Strength and Conditioning, Pozna\u0144 University of Physical Education","place":["Pozna\u0144, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Witold","family":"K\u0119dzia","sequence":"additional","affiliation":[{"name":"Division of Gynecology, Department of Gynecology, Center of General Sexology and Sexology of Developmental Age, Poznan University of Medical Sciences","place":["Poznan, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"Opydo-Szymaczek","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Poznan University of Medical Sciences","place":["Poznan, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"3041","DOI":"10.3390\/jcm9093041","article-title":"Risk factors of overweight and obesity related to diet and disordered eating attitudes in adolescent girls with clinical features of polycystic ovary syndrome","volume":"9","author":"Mizgier","year":"2020","journal-title":"J Clin Med"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"896","DOI":"10.3390\/nu13030896","article-title":"Relation between inflammation, oxidative stress, and macronutrient intakes in normal and excessive body weight adolescent girls with clinical features of PCOS","volume":"13","author":"Mizgier","year":"2021","journal-title":"Nutrients"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"3469","DOI":"10.3390\/jcm10163469","article-title":"Dietary and physical activity habits in adolescent girls with polycystic ovary syndrome (PCOS)-HA study","volume":"10","author":"Mizgier","year":"2021","journal-title":"J Clin Med"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"100193","DOI":"10.1016\/j.advnut.2024.100193","article-title":"Prevalence and etiology of eating disorders in polycystic ovary syndrome: a scoping review","volume":"15","author":"Lalonde-Bester","year":"2024","journal-title":"Adv Nutr"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.3390\/nu17071190","article-title":"Risk factors of primary dysmenorrhea in female adolescent basketball players related to dietary, hormonal, and immuno-metabolic factors and disordered eating attitudes","volume":"17","author":"Mizgier","year":"2025","journal-title":"Nutrients"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"3525","DOI":"10.1038\/s41598-024-54100-1","article-title":"Effects of AIDiet intervention to improve diet quality, immuno-metabolic health in normal and overweight PCOS girls: a pilot study","volume":"14","author":"Mizgier","year":"2024","journal-title":"Sci Rep"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"112449","DOI":"10.1016\/j.exger.2024.112449","article-title":"Associated between cognition, brain-derived neurotrophic factor (BDNF) and macronutrients in normal and overweight postmenopausal women","volume":"192","author":"Mruczyk","year":"2024","journal-title":"Exp Gerontol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1188672","DOI":"10.3389\/fncel.2023.1188672","article-title":"Brain-derived neurotrophic factor (BDNF) has direct anti-inflammatory effects on microglia","volume":"17","author":"Charlton","year":"2023","journal-title":"Front Cell Neurosci"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"102955","DOI":"10.1016\/j.arr.2025.102955","article-title":"The muscle-brain axis in type 2 diabetes: molecular pathways linking sarcopenia and cognitive decline","volume":"113","author":"Xenos","year":"2026","journal-title":"Ageing Res Rev"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.3390\/biology11071063","article-title":"Is brain-derived neurotrophic factor a metabolic hormone in peripheral tissues?","volume":"11","author":"Iu","year":"2022","journal-title":"Biology (Basel)"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e0186384","DOI":"10.1371\/journal.pone.0186384","article-title":"The association between serum brain-derived neurotrophic factor and a cluster of cardiovascular risk factors in adolescents: the CHAMPS-study DK","volume":"12","author":"Pedersen","year":"2017","journal-title":"PLoS One"},{"key":"ref12","first-page":"193","article-title":"Serum levels of BDNF in women with metabolic syndrome and metabolically healthy obese women","volume":"3","author":"Koleva","year":"2022","journal-title":"Endocrinologia"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e20230012","DOI":"10.1590\/1980-5764-DN-2023-0012","article-title":"Brain-derived neurotrophic factor interplay with oxidative stress: neuropathology approach in potential biomarker of Alzheimer\u2019s disease","volume":"17","author":"Shen","year":"2023","journal-title":"Dement Neuropsychol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"204","DOI":"10.59566\/IJBS.2008.4204","article-title":"Increase in levels of BDNF is associated with inflammation and oxidative stress during cardiopulmonary bypass","volume":"4","author":"Amoureux","year":"2008","journal-title":"Int J Biomed Sci"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"10809","DOI":"10.1038\/s41598-020-67868-9","article-title":"Plasma BDNF is a more reliable biomarker than erythrocyte omega-3 index for the omega-3 fatty acid enrichment of brain","volume":"10","author":"Sugasini","year":"2020","journal-title":"Sci Rep"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.3390\/nu13041095","article-title":"The effect of omega-3 fatty acids on thromboxane, brain-derived neurotrophic factor, homocysteine, and vitamin D in depressive children and adolescents: randomized controlled trial","volume":"13","author":"Paduchov\u00e1","year":"2021","journal-title":"Nutrients"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1080\/1028415X.2023.2245996","article-title":"A systematic review and meta-analysis of the omega-3 fatty acids effects on brain-derived neurotrophic factor (BDNF)","volume":"27","author":"Ziaei","year":"2024","journal-title":"Nutr Neurosci"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s40795-025-01174-3","article-title":"The effect of dietary interventions on brain-derived neurotrophic factor (BDNF) levels in adults: a systematic review of clinical trials","volume":"12","author":"Mohamadinarab","year":"2026","journal-title":"BMC Nutr"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1186\/s13048-023-01288-x","article-title":"The effect of calorie restriction along with thylakoid membranes of spinach on the gut-brain axis pathway and oxidative stress biomarkers in obese women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled clinical trial","volume":"16","author":"Nikrad","year":"2023","journal-title":"J Ovarian Res"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"E568","DOI":"10.1503\/jpn.210049","article-title":"BDNF levels in adolescent patients with anorexia nervosa increase continuously to supranormal levels 2.5 years after first hospitalization","volume":"46","author":"Borsdorf","year":"2021","journal-title":"J Psychiatry Neurosci"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"nuaf308","DOI":"10.1093\/nutrit\/nuaf308","article-title":"Effects of dietary weight loss on brain-derived neurotrophic factor in individuals with overweight and obesity: a systematic review","author":"Ashtary-Larky","year":"2026","journal-title":"Nutr Rev"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e0163037","DOI":"10.1371\/journal.pone.0163037","article-title":"The effect of exercise training on resting concentrations of peripheral brain-derived neurotrophic factor (BDNF): a meta-analysis","volume":"11","author":"Dinoff","year":"2016","journal-title":"PLoS One"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"253","DOI":"10.3390\/sports13080253","article-title":"Exercise as modulator of brain-derived neurotrophic factor in adolescents: a systematic review of randomized controlled trials","volume":"13","author":"Rico-Gonz\u00e1lez","year":"2025","journal-title":"Sports"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1275924","DOI":"10.3389\/fnmol.2023.1275924","article-title":"Molecular mechanisms underlying physical exercise-induced brain BDNF overproduction","volume":"16","author":"Cefis","year":"2023","journal-title":"Front Mol Neurosci"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1477992","DOI":"10.3389\/fnut.2025.1477992","article-title":"The correlations between serum bone biomarkers and those related to metabolic and hormonal profile, low-grade inflammation and redox balance, in lean and overweight PCOS adolescent girls","volume":"12","author":"Mizgier","year":"2025","journal-title":"Front Nutr"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1007\/s00784-020-03456-5","article-title":"Subgingival microflora in adolescent females with polycystic ovary syndrome and its association with oral hygiene, gingivitis, and selected metabolic and hormonal parameters","volume":"25","author":"Wendland","year":"2021","journal-title":"Clin Oral Investig"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1079\/phn2005898","article-title":"The international physical activity questionnaire (IPAQ): a study of concurrent and construct validity","volume":"9","author":"Hagstr\u00f6mer","year":"2006","journal-title":"Public Health Nutr"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1249\/01.MSS.0000078924.61453.FB","article-title":"International physical activity questionnaire: 12-country reliability and validity","volume":"35","author":"Craig","year":"2003","journal-title":"Med Sci Sports Exerc"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1249\/MSS.0b013e31821ece12","article-title":"2011 compendium of physical activities: update of codes and MET values","volume":"43","author":"Ainsworth","year":"2011","journal-title":"Med Sci Sports Exerc"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.ejim.2015.11.026","article-title":"Uric acid in metabolic syndrome: from an innocent bystander to a central player","volume":"29","author":"Kanbay","year":"2016","journal-title":"Eur J Intern Med"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1080\/15257770802138558","article-title":"Uric acid: the oxidant-antioxidant paradox","volume":"27","author":"Sautin","year":"2008","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1007\/s00125-006-0537-4","article-title":"Brain-derived neurotrophic factor (BDNF) and type 2 diabetes","volume":"50","author":"Krabbe","year":"2007","journal-title":"Diabetologia"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1016\/j.metabol.2006.02.012","article-title":"Serum brain-derived neurotrophic factor level is increased and associated with obesity in newly diagnosed female patients with type 2 diabetes mellitus","volume":"55","author":"Suwa","year":"2006","journal-title":"Metabolism"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e5260","DOI":"10.1097\/MD.0000000000005260","article-title":"Relationship between body weight and the increment in serum brain-derived neurotrophic factor after oral glucose challenge in men with obesity and metabolic syndrome: a prospective study","volume":"95","author":"Lee","year":"2016","journal-title":"Medicine (Baltimore)"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1007\/s00406-025-01984-","article-title":"The associations of brain-derived neurotrophic factor (BDNF) levels with psychopathology and lipid metabolism parameters in adolescents with major depressive disorder","volume":"276","author":"Liu","year":"2026","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.jpsychires.2014.10.003","article-title":"A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor","volume":"60","author":"Szuhany","year":"2015","journal-title":"J Psychiatr Res"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"241","DOI":"10.3109\/09513590.2011.613969","article-title":"Polycystic ovary syndrome: brain-derived neurotrophic factor (BDNF) plasma and follicular fluid levels","volume":"28","author":"Russo","year":"2012","journal-title":"Gynecol Endocrinol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1037\/a0014501.","article-title":"Endocrine regulation of cognition and neuroplasticity: our pursuit to unveil the complex interaction between hormones, the brain, and behaviour","volume":"62","author":"Galea","year":"2008","journal-title":"Can J Exp Psychol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1210\/en.2009-1036","article-title":"Androgen regulates brain-derived neurotrophic factor in spinal motoneurons and their target musculature","volume":"151","author":"Verhovshek","year":"2010","journal-title":"Endocrinology"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1159\/000526418","article-title":"Use of high-dose androgens is associated with reduced brain-derived neurotrophic factor in male weightlifters","volume":"113","author":"Bj\u00f8rnebekk","year":"2023","journal-title":"Neuroendocrinology"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"107192","DOI":"10.1016\/j.psyneuen.2024.10719","article-title":"Dynamic interplay of cortisol and BDNF in males under acute and chronic psychosocial stress\u2013a randomized controlled study","volume":"170","author":"Herhaus","year":"2024","journal-title":"Psychoneuroendocrinology"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"100784","DOI":"10.1016\/j.yfrne.2019.100784","article-title":"BDNF and cortisol integrative system\u2014plasticity vs. degeneration: implications of the Val66Met polymorphism","volume":"55","author":"de Assis","year":"2019","journal-title":"Front Neuroendocrinol"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.nbd.2010.04.017","article-title":"An inverse relationship between cortisol and BDNF levels in schizophrenia: data from human postmortem and animal studies","volume":"39","author":"Issa","year":"2010","journal-title":"Neurobiol"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1590\/s1516-44462003000400010","article-title":"Update on stress and depression: the role of the hypothalamic-pituitary-adrenal (HPA) axis","volume":"25","author":"Mello","year":"2003","journal-title":"Rev Bras Psiquiatr"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"2520","DOI":"10.4103\/NRR.NRR-D-24-00355","article-title":"Glucocorticoid receptor signaling in the brain and its involvement in cognitive function","volume":"20","author":"Su","year":"2025","journal-title":"Neural Regen Res"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"392","DOI":"10.3389\/fncel.2015.00392","article-title":"Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders","volume":"9","author":"Kelly","year":"2015","journal-title":"Front Cell Neurosci"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"674106","DOI":"10.1155\/2013\/674106","article-title":"Gut microbiota, microinflammation, metabolic profile, and zonulin concentration in obese and normal weight subjects","volume":"2013","author":"Zak-Go\u0142\u0105b","year":"2013","journal-title":"Int J Endocrinol"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"e37160","DOI":"10.1371\/journal.pone.003716","article-title":"Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance","volume":"7","author":"Moreno-Navarrete","year":"2012","journal-title":"PLoS One"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"268","DOI":"10.3945\/an.113.005280","article-title":"\u03a9-3 fatty acid supplementation as a potential therapeutic aid for the recovery from mild traumatic brain injury\/concussion","volume":"5","author":"Barrett","year":"2014","journal-title":"Adv Nutr"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1830074\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:43:49Z","timestamp":1779342229000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1830074\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,21]]},"references-count":49,"alternative-id":["10.3389\/fnut.2026.1830074"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1830074","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,21]]},"article-number":"1830074"}}