{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T05:10:14Z","timestamp":1793337014174,"version":"4.5.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"The International Hundred Thousand Plus Cohort Consortium"},{"DOI":"10.13039\/100006458","name":"Children\u2019s Hospital of Philadelphia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006458","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-26217-4","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T12:51:40Z","timestamp":1764161500000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pro\u2011inflammatory insulin\u2011resistant lipid phenotype in down syndrome identified by 1H\u2011NMR metabolomics in obesity-matched African\u2011American children and young adults"],"prefix":"10.1038","volume":"15","author":[{"given":"Hui-Qi","family":"Qu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Connolly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garnet","family":"Eister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Mentch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Glessner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakon","family":"Hakonarson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"26217_CR1","doi-asserted-by":"publisher","first-page":"2917","DOI":"10.1007\/s00204-016-1843-3","volume":"90","author":"F Copped\u00e8","year":"2016","unstructured":"Copped\u00e8, F. Risk factors for down syndrome. Arch. Toxicol. 90, 2917\u20132929 (2016).","journal-title":"Arch. Toxicol."},{"key":"26217_CR2","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1111\/j.1741-1130.2010.00249.x","volume":"7","author":"J Torr","year":"2010","unstructured":"Torr, J., Strydom, A., Patti, P. & Jokinen, N. Aging in down syndrome: morbidity and mortality. J. Policy Pract. Intellect. Disabil. 7, 70\u201381 (2010).","journal-title":"J. Policy Pract. Intellect. Disabil."},{"issue":"2","key":"26217_CR3","doi-asserted-by":"publisher","first-page":"e20190137","DOI":"10.1542\/peds.2019-0137","volume":"144","author":"SN Magge","year":"2019","unstructured":"Magge, S. N., Zemel, B. S., Pipan, M. E., Gidding, S. S. & Kelly, A. Cardiometabolic risk and body composition in youth with down syndrome. Pediatrics 144(2), e20190137 (2019).","journal-title":"Pediatrics"},{"key":"26217_CR4","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.ridd.2016.06.018","volume":"57","author":"F Bertapelli","year":"2016","unstructured":"Bertapelli, F., Pitetti, K., Agiovlasitis, S. & Guerra-Junior, G. Overweight and obesity in children and adolescents with down syndrome\u2014prevalence, determinants, consequences, and interventions: A literature review. Res. Dev. Disabil. 57, 181\u2013192. https:\/\/doi.org\/10.1016\/j.ridd.2016.06.018 (2016).","journal-title":"Res. Dev. Disabil."},{"key":"26217_CR5","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.jpeds.2017.05.077","volume":"189","author":"D Valentini","year":"2017","unstructured":"Valentini, D. et al. Nonalcoholic fatty liver disease in italian children with down syndrome: prevalence and correlation with obesity-related features. J. Pediatrics 189, 92\u201397 (2017).","journal-title":"J. Pediatrics"},{"key":"26217_CR6","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1111\/jch.12890","volume":"19","author":"P Parra","year":"2017","unstructured":"Parra, P., Costa, R., de As\u00faa, D. R., Moldenhauer, F. & Su\u00e1rez, C. Atherosclerotic surrogate markers in adults with down syndrome: A Case-Control study. J. Clin. Hypertens. 19, 205\u2013211. https:\/\/doi.org\/10.1111\/jch.12890 (2017).","journal-title":"J. Clin. Hypertens."},{"key":"26217_CR7","doi-asserted-by":"publisher","first-page":"2892","DOI":"10.2337\/dc22-0482","volume":"45","author":"AA Aslam","year":"2022","unstructured":"Aslam, A. A. et al. Diabetes and obesity in down syndrome across the lifespan: A retrospective cohort study using UK electronic health records. Diabetes Care. 45, 2892\u20132899 (2022).","journal-title":"Diabetes Care"},{"key":"26217_CR8","doi-asserted-by":"publisher","first-page":"18","DOI":"10.2174\/1567205012666151020114607","volume":"13","author":"E Head","year":"2016","unstructured":"Head, E., Lott, T. & Wilcock, I. M. A Lemere, C. Aging in down syndrome and the development of alzheimer\u2019s disease neuropathology. Curr. Alzheimer Res. 13, 18\u201329 (2016).","journal-title":"Curr. Alzheimer Res."},{"issue":"2","key":"26217_CR9","first-page":"2021","volume":"9","author":"M Moreau","year":"2021","unstructured":"Moreau, M. et al. Metabolic diseases and Down Syndrome: How Are They Linked Together?. Biomed 9(2), 2021 (2021).","journal-title":"Biomed"},{"key":"26217_CR10","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1194\/jlr.M600542-JLR200","volume":"48","author":"GH Tansley","year":"2007","unstructured":"Tansley, G. H. et al. The cholesterol transporter ABCG1 modulates the subcellular distribution and proteolytic processing of \u03b2-amyloid precursor protein. J. Lipid Res. 48, 1022\u20131034 (2007).","journal-title":"J. Lipid Res."},{"issue":"3","key":"26217_CR11","doi-asserted-by":"publisher","first-page":"e20172151","DOI":"10.1542\/peds.2017-2151","volume":"140","author":"AP Hardin","year":"2017","unstructured":"Hardin, A. P. et al. Age limit of pediatrics. Pediatrics 140(3), e20172151 (2017).","journal-title":"Pediatrics"},{"key":"26217_CR12","unstructured":"Balasundaram, P. & Krishna, S. In StatPearls (StatPearls Publishing Copyright \u00a9 2025 (StatPearls Publishing LLC., 2025)."},{"key":"26217_CR13","unstructured":"Weir, C. B. & Jan, A. In StatPearls (StatPearls Publishing Copyright \u00a9 2025 (StatPearls Publishing LLC., 2025)."},{"key":"26217_CR14","doi-asserted-by":"publisher","first-page":"e1204","DOI":"10.1542\/peds.2015-1652","volume":"136","author":"BS Zemel","year":"2015","unstructured":"Zemel, B. S. et al. Growth charts for children with down syndrome in the united States. Pediatrics 136, e1204\u20131211. https:\/\/doi.org\/10.1542\/peds.2015-1652 (2015).","journal-title":"Pediatrics"},{"issue":"6","key":"26217_CR15","doi-asserted-by":"crossref","first-page":"406","DOI":"10.3390\/metabo15060406","volume":"15","author":"HQ Qu","year":"2025","unstructured":"Qu, H. Q., Connolly, J. J., Mentch, F., Glessner, J. & Hakonarson, H. Metabolic remodeling and the modulatory role of vitamin d deficiency in african american children and adolescents with obesity. Metabolites 15(6), 406 (2025).","journal-title":"Metabolites"},{"key":"26217_CR16","unstructured":"Nightingale. Biomarker quantification version 2020."},{"key":"26217_CR17","first-page":"192","volume":"8","author":"P Soininen","year":"2015","unstructured":"Soininen, P., Kangas, A. J., W\u00fcrtz, P., Suna, T. & Ala-Korpela, M. Quantitative serum nuclear magnetic resonance metabolomics in cardiovascular epidemiology and genetics. Circulation: Cardiovasc. Genet. 8, 192\u2013206 (2015).","journal-title":"Circulation: Cardiovasc. Genet."},{"key":"26217_CR18","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1093\/aje\/kwx016","volume":"186","author":"P W\u00fcrtz","year":"2017","unstructured":"W\u00fcrtz, P. et al. Quantitative serum nuclear magnetic resonance metabolomics in large-scale epidemiology: a primer on-omic technologies. Am. J. Epidemiol. 186, 1084\u20131096 (2017).","journal-title":"Am. J. Epidemiol."},{"key":"26217_CR19","unstructured":"Core Team, R. R. R: A language and environment for statistical computing. (2013)."},{"key":"26217_CR20","unstructured":"Van Rossum, G. & Drake, F. L. Jr The python language reference. Python Software Foundation: Wilmington, DE, USA (2014)."},{"key":"26217_CR21","first-page":"2825","volume":"12","author":"F Pedregosa","year":"2011","unstructured":"Pedregosa, F. et al. Scikit-learn: machine learning in python. J. Mach. Learn. Res. 12, 2825\u20132830 (2011).","journal-title":"J. Mach. Learn. Res."},{"key":"26217_CR22","doi-asserted-by":"publisher","first-page":"3526","DOI":"10.1039\/C8AN00599K","volume":"143","author":"LC Lee","year":"2018","unstructured":"Lee, L. C., Liong, C. Y. & Jemain, A. A. Partial least squares-discriminant analysis (PLS-DA) for classification of high-dimensional (HD) data: a review of contemporary practice strategies and knowledge gaps. Analyst 143, 3526\u20133539 (2018).","journal-title":"Analyst"},{"key":"26217_CR23","doi-asserted-by":"publisher","first-page":"3299","DOI":"10.1194\/jlr.M009449","volume":"51","author":"O Quehenberger","year":"2010","unstructured":"Quehenberger, O. et al. Lipidomics reveals a remarkable diversity of lipids in human plasma. J. Lipid Res. 51, 3299\u20133305 (2010).","journal-title":"J. Lipid Res."},{"key":"26217_CR24","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1002\/oby.21448","volume":"24","author":"KT Tonks","year":"2016","unstructured":"Tonks, K. T. et al. Skeletal muscle and plasma lipidomic signatures of insulin resistance and overweight\/obesity in humans. Obesity 24, 908\u2013916 (2016).","journal-title":"Obesity"},{"key":"26217_CR25","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.tjnut.2023.08.037","volume":"154","author":"M Martin","year":"2024","unstructured":"Martin, M. et al. Impaired reverse cholesterol transport is associated with changes in fatty acid profile in children and adolescents with abdominal obesity. J. Nutr. 154, 12\u201325 (2024).","journal-title":"J. Nutr."},{"key":"26217_CR26","doi-asserted-by":"publisher","first-page":"200","DOI":"10.12997\/jla.2025.14.2.200","volume":"14","author":"B Davico","year":"2025","unstructured":"Davico, B. et al. Fatty acids in childhood obesity: A link between Nutrition, metabolic alterations and cardiovascular risk. J. Lipid Atherosclerosis. 14, 200 (2025).","journal-title":"J. Lipid Atherosclerosis"},{"key":"26217_CR27","first-page":"1469","volume":"1863","author":"P S\u00e1nchez-Aguilera","year":"2018","unstructured":"S\u00e1nchez-Aguilera, P. et al. Role of ABCA1 on membrane cholesterol content, insulin-dependent Akt phosphorylation and glucose uptake in adult skeletal muscle fibers from mice. Biochim. Et Biophys. Acta (BBA)-Molecular Cell. Biology Lipids. 1863, 1469\u20131477 (2018).","journal-title":"Biochim. Et Biophys. Acta (BBA)-Molecular Cell. Biology Lipids"},{"key":"26217_CR28","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1210\/jc.2015-3525","volume":"101","author":"S Rauschert","year":"2016","unstructured":"Rauschert, S. et al. Lipidomics reveals associations of phospholipids with obesity and insulin resistance in young adults. J. Clin. Endocrinol. Metabolism. 101, 871\u2013879 (2016).","journal-title":"J. Clin. Endocrinol. Metabolism"},{"key":"26217_CR29","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1002\/j.2040-4603.2013.tb00517.x","volume":"3","author":"JY Chiang","year":"2013","unstructured":"Chiang, J. Y. Bile acid metabolism and signaling. Compr. Physiol. 3, 1191 (2013).","journal-title":"Compr. Physiol."},{"key":"26217_CR30","doi-asserted-by":"publisher","first-page":"143","DOI":"10.5114\/pedm.2023.131162","volume":"29","author":"M Hetman","year":"2023","unstructured":"Hetman, M. et al. Predisposition to atherosclerosis in children and adults with trisomy 21: biochemical and metabolomic studies. Pediatr. Endocrinol. Diabetes Metabolism. 29, 143\u2013155 (2023).","journal-title":"Pediatr. Endocrinol. Diabetes Metabolism"},{"key":"26217_CR31","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1016\/j.ecl.2008.09.002","volume":"37","author":"C Lara-Castro","year":"2008","unstructured":"Lara-Castro, C. & Garvey, W. T. Intracellular lipid accumulation in liver and muscle and the insulin resistance syndrome. Endocrinol. Metab. Clin. North Am. 37, 841\u2013856 (2008).","journal-title":"Endocrinol. Metab. Clin. North Am."},{"key":"26217_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/j.2040-4603.2018.tb00008.x","volume":"8","author":"M Alves-Bezerra","year":"2018","unstructured":"Alves-Bezerra, M. & Cohen, D. E. Triglyceride metabolism in the liver. Compr. Physiol. 8, 1\u201322 (2018).","journal-title":"Compr. Physiol."},{"key":"26217_CR33","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1007\/s00125-005-0125-z","volume":"49","author":"M Adiels","year":"2006","unstructured":"Adiels, M. et al. Overproduction of large VLDL particles is driven by increased liver fat content in man. Diabetologia 49, 755\u2013765 (2006).","journal-title":"Diabetologia"},{"key":"26217_CR34","doi-asserted-by":"crossref","unstructured":"Morton, R. E., Mihna, D. & Liu, Y. The lipid substrate preference of CETP controls the biochemical properties of HDL in fat\/cholesterol-fed hamsters. Journal Lipid Research 62 (2021).","DOI":"10.1016\/j.jlr.2021.100027"},{"key":"26217_CR35","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1038\/nrm.2017.138","volume":"19","author":"T Harayama","year":"2018","unstructured":"Harayama, T. & Riezman, H. Understanding the diversity of membrane lipid composition. Nat. Rev. Mol. Cell Biol. 19, 281\u2013296 (2018).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"26217_CR36","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1016\/j.jnutbio.2013.02.009","volume":"24","author":"B Ruiz-N\u00fa\u00f1ez","year":"2013","unstructured":"Ruiz-N\u00fa\u00f1ez, B., Pruimboom, L., Dijck-Brouwer, D. J. & Muskiet, F. A. Lifestyle and nutritional imbalances associated with Western diseases: causes and consequences of chronic systemic low-grade inflammation in an evolutionary context. J. Nutr. Biochem. 24, 1183\u20131201 (2013).","journal-title":"J. Nutr. Biochem."},{"key":"26217_CR37","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/S0021-9150(99)00495-5","volume":"152","author":"DS Freedman","year":"2000","unstructured":"Freedman, D. S., Bowman, B. A., Otvos, J. D., Srinivasan, S. R. & Berenson, G. S. Levels and correlates of LDL and VLDL particle sizes among children: the Bogalusa heart study. Atherosclerosis 152, 441\u2013449 (2000).","journal-title":"Atherosclerosis"},{"key":"26217_CR38","doi-asserted-by":"publisher","first-page":"e2421724","DOI":"10.1001\/jamanetworkopen.2024.21724","volume":"7","author":"AM Thompson-Paul","year":"2024","unstructured":"Thompson-Paul, A. M. et al. Pediatric lipid screening prevalence using nationwide electronic medical records. JAMA Netw. Open. 7, e2421724. https:\/\/doi.org\/10.1001\/jamanetworkopen.2024.21724 (2024).","journal-title":"JAMA Netw. Open."},{"key":"26217_CR39","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1111\/jir.13128","volume":"68","author":"C Gastelum Guerrero","year":"2024","unstructured":"Gastelum Guerrero, C. et al. A systematic review and meta-analysis of serum lipid concentrations in people with down syndrome. J. Intellect. Disabil. Res. 68, 553\u2013563 (2024).","journal-title":"J. Intellect. Disabil. Res."},{"key":"26217_CR40","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1038\/s41467-023-36231-7","volume":"14","author":"H Julkunen","year":"2023","unstructured":"Julkunen, H. et al. Atlas of plasma NMR biomarkers for health and disease in 118,461 individuals from the UK biobank. Nat. Commun. 14, 604 (2023).","journal-title":"Nat. Commun."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-26217-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-26217-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-26217-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T12:51:43Z","timestamp":1764161503000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-26217-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["26217"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-26217-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,26]]},"assertion":[{"value":"20 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study was approved by the Institutional Review Board (IRB) of the Children\u2019s Hospital of Philadelphia and conducted in accordance with the Declaration of Helsinki, the U.S. Common Rule (45 CFR 46), and all applicable institutional guidelines for pediatric and vulnerable populations. Human participants and personal information are all encrypted to ensure no PHI are included and study participants are de-identified. All human subjects or their proxies provided written informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"All authors have provided consent for publication of the manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"42039"}}