{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T12:23:10Z","timestamp":1784031790673,"version":"3.55.0"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T00:00:00Z","timestamp":1735344000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T00:00:00Z","timestamp":1735344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Williams Syndrome (WS) is a rare neurodevelopmental disorder with a prevalence of 1 in 7500 to 1 in 20,000 individuals, caused by a microdeletion in chromosome 7q11.23. Despite its distinctive clinical features, the underlying metabolic alterations remain largely unexplored. This study employs targeted metabolomics to investigate the metabolic characteristics of children with WS. Using liquid chromatography-tandem mass spectrometry (LC-MS\/MS), we identified significant dysregulation of 15 metabolites, with 11 upregulated and 4 downregulated. Notably, amino acids such as alanine, proline, and arginine were significantly elevated. Fatty acid metabolism showed pronounced upregulation of long-chain saturated fatty acids (C18:0, C20:0, C22:0, C24:0, C26:0, and C28:0) and downregulation of long-chain unsaturated fatty acids (C18:2 LA, C22:6 DHA, C16:1 PLA, and t-C18:1 EA), except for upregulated nervonic acid (C24:1) and arachidonic acid (C20:4). Metabolic pathway analysis highlighted disruptions in arginine synthesis, arginine\/proline metabolism, alanine, aspartate and glutamate metabolism, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and arachidonic acid metabolism. This study provides the first comprehensive analysis of amino acid and fatty acid metabolism in children with WS, offering insights into the disorder\u2019s complex metabolic landscape. Further validation in larger cohorts is essential to confirm these findings and their potential as biomarkers and therapeutic targets.<\/jats:p>","DOI":"10.1038\/s41598-024-83146-4","type":"journal-article","created":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T08:44:04Z","timestamp":1735375444000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Metabolic profiling reveals altered amino acid and fatty acid metabolism in children with Williams Syndrome"],"prefix":"10.1038","volume":"14","author":[{"given":"Weijun","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changxuan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chai","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingping","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaochun","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,28]]},"reference":[{"key":"83146_CR1","first-page":"781","volume":"59","author":"LA Perez Jurado","year":"1996","unstructured":"Perez Jurado, L. A., Peoples, R., Kaplan, P., Hamel, B. C. & Francke, U. Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth. Am. J. Hum. Genet. 59, 781\u2013792 (1996).","journal-title":"Am. J. Hum. Genet."},{"key":"83146_CR2","volume-title":"GeneReviews((R)) (eds M","author":"CA Morris","year":"1993","unstructured":"Morris, C. A. et al. GeneReviews((R)) (eds M (P. Adam, 1993)."},{"key":"83146_CR3","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1111\/j.1469-7610.2008.01887.x","volume":"49","author":"MA Martens","year":"2008","unstructured":"Martens, M. A., Wilson, S. J., Reutens, D. C. & Research Review Williams syndrome: a critical review of the cognitive, behavioral, and neuroanatomical phenotype. J. Child. Psychol. Psychiatry. 49, 576\u2013608. https:\/\/doi.org\/10.1111\/j.1469-7610.2008.01887.x (2008).","journal-title":"J. Child. Psychol. Psychiatry"},{"key":"83146_CR4","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1038\/s41572-021-00276-z","volume":"7","author":"BA Kozel","year":"2021","unstructured":"Kozel, B. A. et al. Williams syndrome. Nat. Rev. Dis. Primers. 7, 42. https:\/\/doi.org\/10.1038\/s41572-021-00276-z (2021).","journal-title":"Nat. Rev. Dis. Primers"},{"key":"83146_CR5","unstructured":"Wilson, M. & Carter, I. B. in StatPearls (2023)."},{"key":"83146_CR6","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1161\/01.cir.24.6.1311","volume":"24","author":"JC Williams","year":"1961","unstructured":"Williams, J. C., Barratt-Boyes, B. G. & Lowe, J. B. Supravalvular aortic stenosis. Circulation 24, 1311\u20131318. https:\/\/doi.org\/10.1161\/01.cir.24.6.1311 (1961).","journal-title":"Circulation"},{"key":"83146_CR7","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1161\/01.cir.26.6.1235","volume":"26","author":"AJ Beuren","year":"1962","unstructured":"Beuren, A. J., Apitz, J. & Harmjanz, D. Supravalvular aortic stenosis in association with mental retardation and a certain facial appearance. Circulation 26, 1235\u20131240. https:\/\/doi.org\/10.1161\/01.cir.26.6.1235 (1962).","journal-title":"Circulation"},{"key":"83146_CR8","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1002\/ajmg.a.31210","volume":"140","author":"A Selicorni","year":"2006","unstructured":"Selicorni, A. et al. Thyroid anomalies in Williams syndrome: investigation of 95 patients. Am. J. Med. Genet. A. 140, 1098\u20131101. https:\/\/doi.org\/10.1002\/ajmg.a.31210 (2006).","journal-title":"Am. J. Med. Genet. A"},{"key":"83146_CR9","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1111\/j.1365-2265.2005.02365.x","volume":"63","author":"S Stagi","year":"2005","unstructured":"Stagi, S. et al. Thyroid function and morphology in patients affected by Williams syndrome. Clin. Endocrinol. (Oxf). 63, 456\u2013460. https:\/\/doi.org\/10.1111\/j.1365-2265.2005.02365.x (2005).","journal-title":"Clin. Endocrinol. (Oxf)"},{"key":"83146_CR10","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1177\/0148607115572833","volume":"40","author":"J Yang","year":"2016","unstructured":"Yang, J., Chang, S. S. & Poon, W. B. Relationship Between Amino Acid and Energy Intake and Long-Term Growth and Neurodevelopmental Outcomes in Very Low Birth Weight Infants. JPEN J. Parenter. Enter. Nutr. 40, 820\u2013826. https:\/\/doi.org\/10.1177\/0148607115572833 (2016).","journal-title":"JPEN J. Parenter. Enter. Nutr."},{"key":"83146_CR11","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1111\/j.1651-2227.2003.tb00662.x","volume":"92","author":"JP Colombo","year":"2003","unstructured":"Colombo, J. P., Garcia-Rodenas, C., Guesry, P. R. & Rey, J. Potential effects of supplementation with amino acids, choline or sialic acid on cognitive development in young infants. Acta Paediatr. Suppl. 92, 42\u201346. https:\/\/doi.org\/10.1111\/j.1651-2227.2003.tb00662.x (2003).","journal-title":"Acta Paediatr. Suppl."},{"key":"83146_CR12","doi-asserted-by":"publisher","unstructured":"Tain, Y. L. & Hsu, C. N. Amino Acids during Pregnancy and Offspring Cardiovascular-Kidney-Metabolic Health. Nutrients 16 https:\/\/doi.org\/10.3390\/nu16091263 (2024).","DOI":"10.3390\/nu16091263"},{"key":"83146_CR13","doi-asserted-by":"publisher","first-page":"e13264","DOI":"10.1111\/mcn.13264","volume":"18","author":"P Parikh","year":"2022","unstructured":"Parikh, P. et al. Animal source foods, rich in essential amino acids, are important for linear growth and development of young children in low- and middle-income countries. Matern Child. Nutr. 18, e13264. https:\/\/doi.org\/10.1111\/mcn.13264 (2022).","journal-title":"Matern Child. Nutr."},{"key":"83146_CR14","doi-asserted-by":"publisher","first-page":"e0154715","DOI":"10.1371\/journal.pone.0154715","volume":"11","author":"T Jumbe","year":"2016","unstructured":"Jumbe, T. et al. Whole Blood Levels of the n-6 Essential Fatty Acid Linoleic Acid Are Inversely Associated with Stunting in 2-to-6 Year Old Tanzanian Children: A Cross-Sectional Study. PLoS One. 11, e0154715. https:\/\/doi.org\/10.1371\/journal.pone.0154715 (2016).","journal-title":"PLoS One"},{"key":"83146_CR15","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/s41569-022-00760-3","volume":"20","author":"RW McGarrah","year":"2023","unstructured":"McGarrah, R. W. & White, P. J. Branched-chain amino acids in cardiovascular disease. Nat. Rev. Cardiol. 20, 77\u201389. https:\/\/doi.org\/10.1038\/s41569-022-00760-3 (2023).","journal-title":"Nat. Rev. Cardiol."},{"key":"83146_CR16","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1152\/physrev.00003.2018","volume":"99","author":"H Jakubowski","year":"2019","unstructured":"Jakubowski, H. Homocysteine Modification in Protein Structure\/Function and Human Disease. Physiol. Rev. 99, 555\u2013604. https:\/\/doi.org\/10.1152\/physrev.00003.2018 (2019).","journal-title":"Physiol. Rev."},{"key":"83146_CR17","doi-asserted-by":"publisher","unstructured":"Abdelhamid, A. S. et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 3, Cd003177 (2020). https:\/\/doi.org\/10.1002\/14651858.CD003177.pub5","DOI":"10.1002\/14651858.CD003177.pub5"},{"key":"83146_CR18","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1161\/circulationaha.124.069881","volume":"150","author":"V Bittner","year":"2024","unstructured":"Bittner, V. Eicosapentanoic Acid Supplementation for Atherosclerotic Cardiovascular Disease Prevention. Circulation 150, 435\u2013438. https:\/\/doi.org\/10.1161\/circulationaha.124.069881 (2024).","journal-title":"Circulation"},{"key":"83146_CR19","doi-asserted-by":"publisher","unstructured":"Zhou, Y., Khan, H., Xiao, J. & Cheang, W. S. Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease. Int. J. Mol. Sci. 22 https:\/\/doi.org\/10.3390\/ijms222112029 (2021).","DOI":"10.3390\/ijms222112029"},{"key":"83146_CR20","doi-asserted-by":"publisher","unstructured":"Birch, E. E., Garfield, S., Hoffman, D. R., Uauy, R. & Birch, D. G. A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants. Dev. Med. Child. Neurol. 42, 174\u2013181. https:\/\/doi.org\/10.1017\/s0012162200000311 (2000).","DOI":"10.1017\/s0012162200000311"},{"key":"83146_CR21","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1080\/10408398.2019.1573800","volume":"60","author":"BP Martins","year":"2020","unstructured":"Martins, B. P., Bandarra, N. M. & Figueiredo-Braga, M. The role of marine omega-3 in human neurodevelopment, including Autism Spectrum Disorders and Attention-Deficit\/Hyperactivity Disorder - a review. Crit. Rev. Food Sci. Nutr. 60, 1431\u20131446. https:\/\/doi.org\/10.1080\/10408398.2019.1573800 (2020).","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"83146_CR22","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1301\/nr.2006.may.s24-s33","volume":"64","author":"R Uauy","year":"2006","unstructured":"Uauy, R. & Dangour, A. D. Nutrition in brain development and aging: role of essential fatty acids. Nutr. Rev. 64, 24\u201333. https:\/\/doi.org\/10.1301\/nr.2006.may.s24-s33 (2006). discussion S72-91.","journal-title":"Nutr. Rev."},{"key":"83146_CR23","doi-asserted-by":"publisher","first-page":"8418","DOI":"10.1038\/s41598-022-11970-7","volume":"12","author":"S Hosseinkhani","year":"2022","unstructured":"Hosseinkhani, S. et al. Targeted metabolomics analysis of amino acids and acylcarnitines as risk markers for diabetes by LC-MS\/MS technique. Sci. Rep. 12, 8418. https:\/\/doi.org\/10.1038\/s41598-022-11970-7 (2022).","journal-title":"Sci. Rep."},{"key":"83146_CR24","doi-asserted-by":"publisher","first-page":"5426","DOI":"10.1002\/anie.200905579","volume":"49","author":"WJ Griffiths","year":"2010","unstructured":"Griffiths, W. J. et al. Targeted metabolomics for biomarker discovery. Angew Chem. Int. Ed. Engl. 49, 5426\u20135445. https:\/\/doi.org\/10.1002\/anie.200905579 (2010).","journal-title":"Angew Chem. Int. Ed. Engl."},{"key":"83146_CR25","doi-asserted-by":"publisher","first-page":"e2200884","DOI":"10.1002\/mnfr.202200884","volume":"67","author":"L Ma","year":"2023","unstructured":"Ma, L. et al. Anti-Inflammatory Effect of Clostridium butyricum-Derived Extracellular Vesicles in Ulcerative Colitis: Impact on Host microRNAs Expressions and Gut Microbiome Profiles. Mol. Nutr. Food Res. 67, e2200884. https:\/\/doi.org\/10.1002\/mnfr.202200884 (2023).","journal-title":"Mol. Nutr. Food Res."},{"key":"83146_CR26","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.ejim.2016.12.015","volume":"38","author":"AP Delitala","year":"2017","unstructured":"Delitala, A. P., Fanciulli, G., Maioli, M. & Delitala, G. Subclinical hypothyroidism, lipid metabolism and cardiovascular disease. Eur. J. Intern. Med. 38, 17\u201324. https:\/\/doi.org\/10.1016\/j.ejim.2016.12.015 (2017).","journal-title":"Eur. J. Intern. Med."},{"key":"83146_CR27","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1210\/clinem\/dgac555","volume":"108","author":"F Shao","year":"2022","unstructured":"Shao, F. et al. Plasma Metabolomics Reveals Systemic Metabolic Alterations of Subclinical and Clinical Hypothyroidism. J. Clin. Endocrinol. Metab. 108, 13\u201325. https:\/\/doi.org\/10.1210\/clinem\/dgac555 (2022).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"83146_CR28","doi-asserted-by":"publisher","unstructured":"Krishnamurthy, H. K. et al. Effect of Micronutrients on Thyroid Parameters. J. Thyroid Res. 2021 (1865483). https:\/\/doi.org\/10.1155\/2021\/1865483 (2021).","DOI":"10.1155\/2021\/1865483"},{"key":"83146_CR29","doi-asserted-by":"publisher","unstructured":"Marchi, M., Galli, G., Magarini, F. M., Mattei, G. & Galeazzi, G. M. Sarcosine as an add-on treatment to antipsychotic medication for people with schizophrenia: a systematic review and meta-analysis of randomized controlled trials. Expert Opin. Drug Metab. Toxicol. 17, 483\u2013493. https:\/\/doi.org\/10.1080\/17425255.2021.1885648 (2021).","DOI":"10.1080\/17425255.2021.1885648"},{"key":"83146_CR30","doi-asserted-by":"publisher","unstructured":"Chang, C. H., Lin, C. H., Liu, C. Y., Chen, S. J. & Lane, H. Y. Efficacy and cognitive effect of sarcosine (N-methylglycine) in patients with schizophrenia: A systematic review and meta-analysis of double-blind randomised controlled trials. J. Psychopharmacol. 34, 495\u2013505. https:\/\/doi.org\/10.1177\/0269881120908016 (2020).","DOI":"10.1177\/0269881120908016"},{"key":"83146_CR31","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1016\/j.biopsych.2003.09.012","volume":"55","author":"G Tsai","year":"2004","unstructured":"Tsai, G., Lane, H. Y., Yang, P., Chong, M. Y. & Lange, N. Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia. Biol. Psychiatry. 55, 452\u2013456. https:\/\/doi.org\/10.1016\/j.biopsych.2003.09.012 (2004).","journal-title":"Biol. Psychiatry"},{"key":"83146_CR32","doi-asserted-by":"publisher","first-page":"4309","DOI":"10.1172\/JCI64801","volume":"123","author":"TJ Wang","year":"2013","unstructured":"Wang, T. J. et al. 2-Aminoadipic acid is a biomarker for diabetes risk. J. Clin. Invest. 123, 4309\u20134317. https:\/\/doi.org\/10.1172\/JCI64801 (2013).","journal-title":"J. Clin. Invest."},{"key":"83146_CR33","doi-asserted-by":"publisher","first-page":"343S","DOI":"10.1093\/ajcn\/71.1.343s","volume":"71","author":"MJ James","year":"2000","unstructured":"James, M. J., Gibson, R. A. & Cleland, L. G. Dietary polyunsaturated fatty acids and inflammatory mediator production. Am. J. Clin. Nutr. 71, 343S\u2013348S. https:\/\/doi.org\/10.1093\/ajcn\/71.1.343s (2000).","journal-title":"Am. J. Clin. Nutr."},{"key":"83146_CR34","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1002\/stem.1620","volume":"32","author":"JX Kang","year":"2014","unstructured":"Kang, J. X., Wan, J. B. & He, C. Concise review: Regulation of stem cell proliferation and differentiation by essential fatty acids and their metabolites. Stem Cells. 32, 1092\u20131098. https:\/\/doi.org\/10.1002\/stem.1620 (2014).","journal-title":"Stem Cells"},{"key":"83146_CR35","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1097\/MCO.0000000000000722","volume":"24","author":"S Ghasemi Fard","year":"2021","unstructured":"Ghasemi Fard, S., Cameron-Smith, D. & Sinclair, A. J. n \u2013\u20093 Docosapentaenoic acid: the iceberg n \u2013\u20093 fatty acid. Curr. Opin. Clin. Nutr. Metab. Care. 24, 134\u2013138. https:\/\/doi.org\/10.1097\/MCO.0000000000000722 (2021).","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"83146_CR36","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/978-1-4020-8831-5_5","volume":"49","author":"JX Kang","year":"2008","unstructured":"Kang, J. X. & Weylandt, K. H. Modulation of inflammatory cytokines by omega-3 fatty acids. Subcell. Biochem. 49, 133\u2013143. https:\/\/doi.org\/10.1007\/978-1-4020-8831-5_5 (2008).","journal-title":"Subcell. Biochem."},{"key":"83146_CR37","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.plefa.2018.03.004","volume":"132","author":"JK Innes","year":"2018","unstructured":"Innes, J. K. & Calder, P. C. Omega-6 fatty acids and inflammation. Prostaglandins Leukot. Essent. Fat. Acids. 132, 41\u201348. https:\/\/doi.org\/10.1016\/j.plefa.2018.03.004 (2018).","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"83146_CR38","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s12993-014-0048-2","volume":"11","author":"GA Mostafa","year":"2015","unstructured":"Mostafa, G. A. & Al-Ayadhi, L. Y. Reduced levels of plasma polyunsaturated fatty acids and serum carnitine in autistic children: relation to gastrointestinal manifestations. Behav. Brain Funct. 11, 4. https:\/\/doi.org\/10.1186\/s12993-014-0048-2 (2015).","journal-title":"Behav. Brain Funct."},{"key":"83146_CR39","doi-asserted-by":"publisher","first-page":"e0156432","DOI":"10.1371\/journal.pone.0156432","volume":"11","author":"N Parletta","year":"2016","unstructured":"Parletta, N., Niyonsenga, T. & Duff, J. Omega-3 and Omega-6 Polyunsaturated Fatty Acid Levels and Correlations with Symptoms in Children with Attention Deficit Hyperactivity Disorder, Autistic Spectrum Disorder and Typically Developing Controls. PLoS One. 11, e0156432. https:\/\/doi.org\/10.1371\/journal.pone.0156432 (2016).","journal-title":"PLoS One"},{"key":"83146_CR40","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.cpr.2014.05.005","volume":"34","author":"E Hawkey","year":"2014","unstructured":"Hawkey, E. & Nigg, J. T. Omega-3 fatty acid and ADHD: blood level analysis and meta-analytic extension of supplementation trials. Clin. Psychol. Rev. 34, 496\u2013505. https:\/\/doi.org\/10.1016\/j.cpr.2014.05.005 (2014).","journal-title":"Clin. Psychol. Rev."},{"key":"83146_CR41","doi-asserted-by":"publisher","first-page":"2730","DOI":"10.3390\/nu6072730","volume":"6","author":"W Stonehouse","year":"2014","unstructured":"Stonehouse, W. Does consumption of LC omega-3 PUFA enhance cognitive performance in healthy school-aged children and throughout adulthood? Evidence from clinical trials. Nutrients 6, 2730\u20132758. https:\/\/doi.org\/10.3390\/nu6072730 (2014).","journal-title":"Nutrients"},{"key":"83146_CR42","doi-asserted-by":"publisher","unstructured":"van der Wurff, I. S. M., Meyer, B. J. & de Groot, R. H. M. Effect of Omega-3 Long Chain Polyunsaturated Fatty Acids (n-3 LCPUFA) Supplementation on Cognition in Children and Adolescents: A Systematic Literature Review with a Focus on n-3 LCPUFA Blood Values and Dose of DHA and EPA. Nutrients 12 https:\/\/doi.org\/10.3390\/nu12103115 (2020).","DOI":"10.3390\/nu12103115"},{"key":"83146_CR43","doi-asserted-by":"publisher","unstructured":"Allegri, L. et al. BAZ1B is a candidate gene responsible for hypothyroidism in Williams syndrome. Eur. J. Med. Genet. 63, 103894. https:\/\/doi.org\/10.1016\/j.ejmg.2020.103894 (2020).","DOI":"10.1016\/j.ejmg.2020.103894"},{"key":"83146_CR44","doi-asserted-by":"publisher","unstructured":"Cooper, R. E., Tye, C., Kuntsi, J., Vassos, E. & Asherson, P. Omega-3 polyunsaturated fatty acid supplementation and cognition: A systematic review and meta-analysis. J. Psychopharmacol. 29, 753\u2013763. https:\/\/doi.org\/10.1177\/0269881115587958 (2015).","DOI":"10.1177\/0269881115587958"},{"key":"83146_CR45","doi-asserted-by":"publisher","unstructured":"Rangel-Huerta, O. D. & Gil, A. Effect of omega-3 fatty acids on cognition: an updated systematic review of randomized clinical trials. Nutr. Rev. 76, 1\u201320. https:\/\/doi.org\/10.1093\/nutrit\/nux064 (2018).","DOI":"10.1093\/nutrit\/nux064"},{"key":"83146_CR46","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1097\/JCP.0000000000000565","volume":"36","author":"G Mazereeuw","year":"2016","unstructured":"Mazereeuw, G. et al. Omega-3 Fatty Acids, Depressive Symptoms, and Cognitive Performance in Patients With Coronary Artery Disease: Analyses From a Randomized, Double-Blind, Placebo-Controlled Trial. J. Clin. Psychopharmacol. 36, 436\u2013444. https:\/\/doi.org\/10.1097\/JCP.0000000000000565 (2016).","journal-title":"J. Clin. Psychopharmacol."},{"key":"83146_CR47","doi-asserted-by":"publisher","first-page":"9797","DOI":"10.1038\/s41598-023-36704-1","volume":"13","author":"F Del Chierico","year":"2023","unstructured":"Del Chierico, F. et al. Analysis of gut microbiota in patients with Williams-Beuren Syndrome reveals dysbiosis linked to clinical manifestations. Sci. Rep. 13, 9797. https:\/\/doi.org\/10.1038\/s41598-023-36704-1 (2023).","journal-title":"Sci. Rep."},{"key":"83146_CR48","doi-asserted-by":"publisher","first-page":"e160","DOI":"10.1002\/imt2.160","volume":"3","author":"L Ma","year":"2024","unstructured":"Ma, L. et al. Clostridium butyricum and carbohydrate active enzymes contribute to the reduced fat deposition in pigs. Imeta 3, e160. https:\/\/doi.org\/10.1002\/imt2.160 (2024).","journal-title":"Imeta"},{"key":"83146_CR49","doi-asserted-by":"publisher","first-page":"2035","DOI":"10.1093\/hmg\/ddaa093","volume":"29","author":"PCR Parrish","year":"2020","unstructured":"Parrish, P. C. R. et al. Whole exome sequencing in patients with Williams-Beuren syndrome followed by disease modeling in mice points to four novel pathways that may modify stenosis risk. Hum. Mol. Genet. 29, 2035\u20132050. https:\/\/doi.org\/10.1093\/hmg\/ddaa093 (2020).","journal-title":"Hum. Mol. Genet."},{"key":"83146_CR50","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/0092-8674(92)90030-g","volume":"68","author":"P Mombaerts","year":"1992","unstructured":"Mombaerts, P. et al. RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68, 869\u2013877. https:\/\/doi.org\/10.1016\/0092-8674(92)90030-g (1992).","journal-title":"Cell"},{"key":"83146_CR51","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1111\/jcpp.12999","volume":"60","author":"R Kimura","year":"2019","unstructured":"Kimura, R. et al. Integrative network analysis reveals biological pathways associated with Williams syndrome. J. Child. Psychol. Psychiatry. 60, 585\u2013598. https:\/\/doi.org\/10.1111\/jcpp.12999 (2019).","journal-title":"J. Child. Psychol. Psychiatry"},{"key":"83146_CR52","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1159\/000074898","volume":"132","author":"TM Stulnig","year":"2003","unstructured":"Stulnig, T. M. Immunomodulation by polyunsaturated fatty acids: mechanisms and effects. Int. Arch. Allergy Immunol. 132, 310\u2013321. https:\/\/doi.org\/10.1159\/000074898 (2003).","journal-title":"Int. Arch. Allergy Immunol."},{"key":"83146_CR53","doi-asserted-by":"publisher","unstructured":"Coniglio, S., Shumskaya, M. & Vassiliou, E. Unsaturated Fatty Acids and Their Immunomodulatory Properties. Biology (Basel). 12. https:\/\/doi.org\/10.3390\/biology12020279 (2023).","DOI":"10.3390\/biology12020279"},{"key":"83146_CR54","doi-asserted-by":"publisher","unstructured":"Gutierrez, S., Svahn, S. L. & Johansson, M. E. Effects of Omega-3 Fatty Acids on Immune Cells. Int. J. Mol. Sci. 20 https:\/\/doi.org\/10.3390\/ijms20205028 (2019).","DOI":"10.3390\/ijms20205028"},{"key":"83146_CR55","doi-asserted-by":"publisher","unstructured":"Fenton, J. I., Hord, N. G., Ghosh, S. & Gurzell, E. A. Immunomodulation by dietary long chain omega-3 fatty acids and the potential for adverse health outcomes. Prostaglandins Leukot. Essent. Fat. Acids. 89, 379\u2013390. https:\/\/doi.org\/10.1016\/j.plefa.2013.09.011 (2013).","DOI":"10.1016\/j.plefa.2013.09.011"},{"key":"83146_CR56","doi-asserted-by":"publisher","unstructured":"Calder, P. C. Immunomodulation by omega-3 fatty acids. Prostaglandins Leukot. Essent. Fat. Acids. 77, 327\u2013335. https:\/\/doi.org\/10.1016\/j.plefa.2007.10.015 (2007).","DOI":"10.1016\/j.plefa.2007.10.015"},{"key":"83146_CR57","doi-asserted-by":"publisher","unstructured":"Pober, B. R. et al. High prevalence of diabetes and pre-diabetes in adults with Williams syndrome. Am. J. Med. Genet. C Semin Med. Genet. 154C, 291\u2013298. https:\/\/doi.org\/10.1002\/ajmg.c.30261 (2010).","DOI":"10.1002\/ajmg.c.30261"},{"key":"83146_CR58","doi-asserted-by":"publisher","unstructured":"Stanley, T. L., Leong, A. & Pober, B. R. Growth, body composition, and endocrine issues in Williams syndrome. Curr. Opin. Endocrinol. Diabetes Obes. 28, 64\u201374. https:\/\/doi.org\/10.1097\/MED.0000000000000588 (2021).","DOI":"10.1097\/MED.0000000000000588"},{"key":"83146_CR59","doi-asserted-by":"publisher","unstructured":"Tillin, T. et al. Diabetes risk and amino acid profiles: cross-sectional and prospective analyses of ethnicity, amino acids and diabetes in a South Asian and European cohort from the SABRE (Southall And Brent REvisited) Study. Diabetologia 58, 968\u2013979. https:\/\/doi.org\/10.1007\/s00125-015-3517-8 (2015).","DOI":"10.1007\/s00125-015-3517-8"},{"key":"83146_CR60","doi-asserted-by":"publisher","unstructured":"Palmer, N. D. et al. Metabolomic profile associated with insulin resistance and conversion to diabetes in the Insulin Resistance Atherosclerosis Study. J. Clin. Endocrinol. Metab. 100, E463\u2013468. https:\/\/doi.org\/10.1210\/jc.2014-2357 (2015).","DOI":"10.1210\/jc.2014-2357"},{"key":"83146_CR61","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1038\/nm.2307","volume":"17","author":"TJ Wang","year":"2011","unstructured":"Wang, T. J. et al. Metabolite profiles and the risk of developing diabetes. Nat. Med. 17, 448\u2013453. https:\/\/doi.org\/10.1038\/nm.2307 (2011).","journal-title":"Nat. Med."},{"key":"83146_CR62","doi-asserted-by":"publisher","first-page":"7010","DOI":"10.1038\/s41598-019-43431-z","volume":"9","author":"S Chen","year":"2019","unstructured":"Chen, S. et al. Serum amino acid profiles and risk of type 2 diabetes among Japanese adults in the Hitachi Health Study. Sci. Rep. 9, 7010. https:\/\/doi.org\/10.1038\/s41598-019-43431-z (2019).","journal-title":"Sci. Rep."},{"key":"83146_CR63","doi-asserted-by":"publisher","unstructured":"Zakaria, N. F., Hamid, M. & Khayat, M. E. Amino Acid-Induced Impairment of Insulin Signaling and Involvement of G-Protein Coupling Receptor. Nutrients 13 https:\/\/doi.org\/10.3390\/nu13072229 (2021).","DOI":"10.3390\/nu13072229"},{"key":"83146_CR64","doi-asserted-by":"publisher","unstructured":"Forouhi, N. G. et al. Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study. Lancet Diabetes Endocrinol. 2, 810\u2013818. https:\/\/doi.org\/10.1016\/S2213-8587(14)70146-9 (2014).","DOI":"10.1016\/S2213-8587(14)70146-9"},{"key":"83146_CR65","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1093\/ajcn\/nqab102","volume":"114","author":"C Luo","year":"2021","unstructured":"Luo, C. et al. The associations between individual plasma SFAs, serine palmitoyl-transferase long-chain base subunit 3 gene rs680379 polymorphism, and type 2 diabetes among Chinese adults. Am. J. Clin. Nutr. 114, 704\u2013712. https:\/\/doi.org\/10.1093\/ajcn\/nqab102 (2021).","journal-title":"Am. J. Clin. Nutr."},{"key":"83146_CR66","doi-asserted-by":"publisher","unstructured":"Lai, K. Z. H. et al. Association of Serum Very-Long-Chain Saturated Fatty Acids With Changes in Insulin Sensitivity and beta-Cell Function: The Prospective Metabolism and Islet Cell Evaluation (PROMISE) Cohort. Diabetes 72, 1664\u20131670. https:\/\/doi.org\/10.2337\/db22-1050 (2023).","DOI":"10.2337\/db22-1050"},{"key":"83146_CR67","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.5551\/jat.39164","volume":"24","author":"K Itcho","year":"2017","unstructured":"Itcho, K. et al. Association between Serum Elaidic Acid Concentration and Insulin Resistance in Two Japanese Cohorts with Different Lifestyles. J. Atheroscler Thromb. 24, 1206\u20131214. https:\/\/doi.org\/10.5551\/jat.39164 (2017).","journal-title":"J. Atheroscler Thromb."},{"key":"83146_CR68","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.biochi.2020.07.021","volume":"177","author":"K Ishibashi","year":"2020","unstructured":"Ishibashi, K. et al. Elaidate, a trans fatty acid, suppresses insulin signaling for glucose uptake in a manner distinct from that of stearate. Biochimie 177, 98\u2013107. https:\/\/doi.org\/10.1016\/j.biochi.2020.07.021 (2020).","journal-title":"Biochimie"},{"key":"83146_CR69","doi-asserted-by":"publisher","unstructured":"Pang, Z. et al. MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights. Nucleic Acids Res. 49, W388\u2013W396. https:\/\/doi.org\/10.1093\/nar\/gkab382 (2021).","DOI":"10.1093\/nar\/gkab382"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-83146-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-83146-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-83146-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T23:03:45Z","timestamp":1735427025000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-83146-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,28]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["83146"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-83146-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,28]]},"assertion":[{"value":"15 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 December 2024","order":3,"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 study was conducted in accordance with the Dec-laration of Helsinki, and approved by the Ethics Committee of the Children\u2019s Hospital Affiliated to Zhejiang University School of Medicine (NO. 2019-IBR-122) on 13 July 2020.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Institutional Review Board Statement"}},{"value":"Informed consent was obtained from all subjects involved in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed Consent"}}],"article-number":"31467"}}