{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T08:40:54Z","timestamp":1760431254554,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:00:00Z","timestamp":1760227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nicolaus Copernicus University in Toru\u0144, Poland","award":["22\/2024\/Debiuty8"],"award-info":[{"award-number":["22\/2024\/Debiuty8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Recent studies suggest that erythroferrone (ERFE), an iron-regulating protein whose primary role is to inhibit hepcidin synthesis, may affect glucose and lipid metabolism, and its serum concentration is reduced in obese and diabetic individuals. The aim of this study was to evaluate the association of ERFE concentration with selected cardiometabolic risk factors in apparently healthy young adults. Methods: This preliminary study consisted of 122 (63 females, 59 males) normoglycemic, non-smoking subjects aged 25\u201340 years. In all participants, anthropometric measurements and the following laboratory tests were performed: fasting plasma glucose, glycated hemoglobin (HbA1c) and serum iron, lipid profile, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), C-reactive protein (CRP), ERFE and hepcidin. Results: The serum ERFE concentration was significantly lower in men compared to women (p = 0.009) and in subjects who were overweight (p &lt; 0.001) and had abdominal obesity (p &lt; 0.001). ERFE showed significant negative correlations with body mass index, waist\u2013hip ratio, HbA1c, CRP, insulin, HOMA-IR and triglycerides. In the logistic regression analysis, ERFE was significantly associated with being overweight (OR = 0.051; p = 0.004), abdominal obesity (OR = 0.372; p &lt; 0.001), HOMA-IR \u2265 2.0 (OR = 0.584; p = 0.013), CRP &gt; 1 mg\/L (OR = 0.648; p = 0.020) and triglycerides (OR = 0.521; p = 0.033). A relevant predominance in the prevalence of cardiometabolic risk factors was observed in subjects with ERFE levels in the first tertile (&lt;1.35 ng\/mL), compared to the third tertile (&gt;2.19 ng\/mL). Conclusions: Serum ERFE is inversely associated with being overweight, increased waist circumference, CRP, and markers of insulin resistance and lipid abnormalities, suggesting its potential relevance as a marker of early cardiometabolic risk in apparently healthy young adults.<\/jats:p>","DOI":"10.3390\/nu17203205","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T07:51:28Z","timestamp":1760428288000},"page":"3205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Association of Serum Erythroferrone, a Regulator of Erythropoiesis and Iron Homeostasis, with Cardiometabolic Risk Factors in Apparently Healthy Young Adults\u2014A Preliminary Study"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9912-0325","authenticated-orcid":false,"given":"Katarzyna","family":"Bergmann","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, 87-100 Toru\u0144, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5295-2236","authenticated-orcid":false,"given":"Anna","family":"Stefa\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, 87-100 Toru\u0144, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2627-7473","authenticated-orcid":false,"given":"Magdalena","family":"Krintus","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, 87-100 Toru\u0144, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/s41366-023-01299-0","article-title":"Iron, glucose and fat metabolism and obesity: An intertwined relationship","volume":"47","author":"Hilton","year":"2023","journal-title":"Int. J. Obes."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1007\/s11154-024-09908-7","article-title":"Iron homeostasis and insulin sensitivity: Unraveling the complex interactions","volume":"25","author":"Sobieska","year":"2024","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11968","DOI":"10.1074\/jbc.M111.336834","article-title":"Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis","volume":"287","author":"Seldin","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/ng.2996","article-title":"Identification of erythroferrone as an erythroid regulator of iron metabolism","volume":"46","author":"Kautz","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.1097\/HS9.0000000000000035","article-title":"Erythroferrone: An Erythroid Regulator of Hepcidin and Iron Metabolism","volume":"2","author":"Coffey","year":"2018","journal-title":"Hemasphere"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e00198","DOI":"10.1097\/BS9.0000000000000198","article-title":"Erythroferrone in focus: Emerging perspectives in iron metabolism and hematopathologies","volume":"6","author":"Babar","year":"2024","journal-title":"Blood Sci."},{"key":"ref_7","unstructured":"(2012). Architect MULTIGENT Iron Assay (6K95) [Package Insert], Abbott Laboratories."},{"key":"ref_8","unstructured":"B\u0105k-Sosnowska, M., Bia\u0142kowska, M., Bogda\u0144ski, P., Chomiuk, T., Dobrowolski, P., Ga\u0142\u0105zka-Sobotka, M., Holecki, M., Jankowska-Zdu\u0144czyk, A., Jarosi\u0144ska, A., and Jezierska, M. (2024). Zalecenia kliniczne dotycz\u0105ce post\u0119powania u chorych na oty\u0142o\u015b\u0107 2024\u2013stanowisko Polskiego Towarzystwa Leczenia Oty\u0142o\u015bci. Med. Prakt. Wyd. Spec., 1\u2013116."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1161\/CIRCULATIONAHA.109.192644","article-title":"Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity","volume":"120","author":"Alberti","year":"2009","journal-title":"Circulation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3912","DOI":"10.1093\/eurheartj\/ehae178","article-title":"2024 ESC Guidelines for the management of elevated blood pressure and hypertension","volume":"45","author":"McEvoy","year":"2024","journal-title":"Eur. Heart J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1001\/jamacardio.2020.0013","article-title":"A New Equation for Calculation of Low-Density Lipoprotein Cholesterol in Patients With Normolipidemia and\/or Hypertriglyceridemia","volume":"5","author":"Sampson","year":"2020","journal-title":"JAMA Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001). Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA, 285, 2486\u20132497.","DOI":"10.1001\/jama.285.19.2486"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1055\/a-0896-8548","article-title":"Circulating Serum Myonectin Levels in Obesity and Type 2 Diabetes Mellitus","volume":"129","author":"Li","year":"2021","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_14","first-page":"P76","article-title":"Plasma Erythroferrone is negatively correlated with total body fat. Society for Endocrinology BES 2022","volume":"86","author":"Hilton","year":"2022","journal-title":"Endocr. Abstr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1177\/0004563220942263","article-title":"Serum myonectin is increased after laparoscopic sleeve gastrectomy","volume":"57","author":"Li","year":"2020","journal-title":"Ann. Clin. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1210\/jc.2017-01604","article-title":"Myonectin Predicts the Development of Type 2 Diabetes","volume":"103","author":"Li","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.clinbiochem.2020.02.001","article-title":"Analytical and biological assessment of circulating human erythroferrone","volume":"79","author":"Appleby","year":"2020","journal-title":"Clin. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1182\/blood-2017-04-777987","article-title":"Immunoassay for human serum erythroferrone","volume":"130","author":"Ganz","year":"2017","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1182\/blood-2023-177943","article-title":"Serum Erythroferrone Levels in a Large General Population: Towards a Better Understanding of Connections between Erythropoiesis and Iron Homeostasis","volume":"142","author":"Busti","year":"2023","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Badenhorst, C.E., Forsyth, A.K., and Govus, A.D. (2022). A contemporary understanding of iron metabolism in active premenopausal females. Front. Sports Act. Living, 4.","DOI":"10.3389\/fspor.2022.903937"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Fillebeen, C., Lam, N.H., Chow, S., Botta, A., Sweeney, G., and Pantopoulos, K. (2020). Regulatory Connections between Iron and Glucose Metabolism. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207773"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Mortera, R., Caccavello, R., Hermo, R., Garay-Sevilla, M.E., and Gugliucci, A. (2021). Higher Hepcidin Levels in Adolescents with Obesity Are Associated with Metabolic Syndrome Dyslipidemia and Visceral Fat. Antioxidants, 10.","DOI":"10.3390\/antiox10050751"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Aguree, S., and Reddy, M.B. (2021). Inflammatory Markers and Hepcidin are Elevated but Serum Iron is Lower in Obese Women of Reproductive Age. Nutrients, 13.","DOI":"10.3390\/nu13010217"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1186\/s12933-024-02377-x","article-title":"Elevated plasma hepcidin concentrations are associated with an increased risk of mortality and nonfatal cardiovascular events in patients with type 2 diabetes: A prospective study","volume":"23","author":"Mantovani","year":"2024","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Martinelli, N., Traglia, M., Campostrini, N., Biino, G., Corbella, M., Sala, C., Busti, F., Masciullo, C., Manna, D., and Previtali, S. (2012). Increased serum hepcidin levels in subjects with the metabolic syndrome: A population study. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048250"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s10020-022-00558-6","article-title":"The role of iron metabolism in chronic diseases related to obesity","volume":"28","author":"Qiu","year":"2022","journal-title":"Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1111\/obr.12057","article-title":"The role of adipocytes in the modulation of iron metabolism in obesity","volume":"14","author":"Coimbra","year":"2013","journal-title":"Obes. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3390\/endocrines4010002","article-title":"Dysmetabolic Iron Overload Syndrome: Going beyond the Traditional Risk Factors Associated with Metabolic Syndrome","volume":"4","author":"Barbalho","year":"2023","journal-title":"Endocrines"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Cempaka, A.R., Tseng, S.-H., Yuan, K.-C., Bai, C.-H., Tinkov, A.A., Skalny, A.V., and Chang, J.-S. (2019). Dysregulated Iron Metabolism-Associated Dietary Pattern Predicts an Altered Body Composition and Metabolic Syndrome. Nutrients, 11.","DOI":"10.3390\/nu11112733"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Yin, W., and Noguchi, C.T. (2025). The Role of Erythropoietin in Metabolic Regulation. Cells, 14.","DOI":"10.3390\/cells14040280"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ebiom.2019.11.007","article-title":"Kidney-secreted erythropoietin lowers lipidemia via activating JAK2-STAT5 signaling in adipose tissue","volume":"50","author":"Li","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1111\/j.1542-4758.2009.00367.x","article-title":"Effect of recombinant human erythropoietin on insulin resistance in hemodialysis patients","volume":"13","author":"Khedr","year":"2009","journal-title":"Hemodial. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e13890","DOI":"10.14814\/phy2.13890","article-title":"Erythroferrone is not required for the glucoregulatory and hematologic effects of chronic erythropoietin treatment in mice","volume":"6","author":"Coffey","year":"2018","journal-title":"Physiol. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Dziembowska, I., W\u00f3jcik, M., Bukowski, J., and \u017bekanowska, E. (2021). Physical Training Increases Erythroferrone Levels in Men. Biology, 10.","DOI":"10.3390\/biology10111215"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Spoto, B., Kakkar, R., Lo, L., Devalaraja, M., Pizzini, P., Torino, C., Leonardis, D., Cutrupi, S., Tripepi, G., and Mallamaci, F. (2019). Serum Erythroferrone Levels Associate with Mortality and Cardiovascular Events in Hemodialysis and in CKD Patients: A Two Cohorts Study. J. Clin. Med., 8.","DOI":"10.3390\/jcm8040523"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Srole, D.N., Jung, G., Waring, A.J., Nemeth, E., and Ganz, T. (2023). Characterization of erythroferrone structural domains relevant to its iron-regulatory function. J. Biol. Chem., 299.","DOI":"10.1016\/j.jbc.2023.105374"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1182\/blood.2021014054","article-title":"Erythroid overproduction of erythroferrone causes iron overload and developmental abnormalities in mice","volume":"139","author":"Coffey","year":"2022","journal-title":"Blood"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/20\/3205\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T07:58:47Z","timestamp":1760428727000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/20\/3205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,12]]},"references-count":37,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["nu17203205"],"URL":"https:\/\/doi.org\/10.3390\/nu17203205","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,12]]}}}