{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T19:00:44Z","timestamp":1782327644441,"version":"3.54.5"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.1038\/s41390-025-04005-0","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T21:03:57Z","timestamp":1742504637000},"page":"1731-1736","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association of DLK1 SNPs with body mass index and plasma lipid levels in children"],"prefix":"10.1038","volume":"98","author":[{"given":"Olga","family":"Pomares","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Laborda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Vales-Villamar\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"P\u00e9rez-Nadador","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco. J.","family":"Mejorado-Molano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Parra-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Mahillo-Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro","family":"Soriano-Guill\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Garc\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"4005_CR1","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1159\/000015259","volume":"84","author":"E Gubina","year":"1999","unstructured":"Gubina, E., Ruiz-Hidalgo, M. J., Baladr\u00f3n, V. & Laborda, J. Assignment of DLK1 to human chromosome band 14q32 by in situ hybridization. Cytogenet. Genome Res. 84, 206\u2013207 (1999).","journal-title":"Cytogenet. Genome Res."},{"key":"4005_CR2","first-page":"119","volume":"15","author":"J Laborda","year":"2000","unstructured":"Laborda, J. The role of the epidermal growth factor-like protein dlk in cell differentiation. Histol. Histopathol. 15, 119\u2013129 (2000).","journal-title":"Histol. Histopathol."},{"key":"4005_CR3","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/0092-8674(93)90252-L","volume":"73","author":"CM Smas","year":"1993","unstructured":"Smas, C. M. & Sul, H. S. Pref-1, a protein containing EGF-like repeats, inhibits adipocyte differentiation. Cell 73, 725\u2013734 (1993).","journal-title":"Cell"},{"key":"4005_CR4","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1046\/j.1432-0436.1999.6420103.x","volume":"64","author":"C Garc\u00e9s","year":"1999","unstructured":"Garc\u00e9s, C., Ruiz-Hidalgo, M. J., Bonvini, E., Goldstein, J. & Laborda, J. Adipocyte differentiation is modulated by secreted delta-like (dlk) variants and requires the expression of membrane-associated dlk. Differentiation 64, 103\u2013114 (1999).","journal-title":"Differentiation"},{"key":"4005_CR5","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1016\/j.jmb.2006.10.043","volume":"367","author":"ML Nueda","year":"2006","unstructured":"Nueda, M. L., Baladron, V., Sanchez-Solana, B., Ballesteros, M. A. & Laborda, J. The EGF-like protein dlk1 inhibits notch signaling and potentiates adipogenesis of mesenchymal cells. J. Mol. Biol. 367, 1281\u20131293 (2006).","journal-title":"J. Mol. Biol."},{"key":"4005_CR6","doi-asserted-by":"publisher","first-page":"5585","DOI":"10.1128\/MCB.22.15.5585-5592.2002","volume":"22","author":"YS Moon","year":"2002","unstructured":"Moon, Y. S. et al. Mice lacking paternally expressed Pref-1\/Dlk1 display growth retardation and accelerated adiposity. Mol. Cell. Biol. 22, 5585\u20135592 (2002).","journal-title":"Mol. Cell. Biol."},{"key":"4005_CR7","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1172\/JCI15924","volume":"111","author":"K Lee","year":"2003","unstructured":"Lee, K. et al. Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor\u20131 (Pref-1). J. Clin. Investig. 111, 453\u2013461 (2003).","journal-title":"J. Clin. Investig."},{"key":"4005_CR8","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1055\/s-0033-1353210","volume":"45","author":"P Kavalkova","year":"2013","unstructured":"Kavalkova, P. et al. Serum preadipocyte factor-1 concentrations in females with obesity and type 2 diabetes mellitus: the influence of very low calorie diet, acute hyperinsulinemia, and fenofibrate treatment. Horm. Metab. Res. 45, 820\u2013826 (2013).","journal-title":"Horm. Metab. Res."},{"key":"4005_CR9","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1111\/dme.12871","volume":"33","author":"SH Lee","year":"2016","unstructured":"Lee, S. H. et al. Serum preadipocyte factor 1 concentrations and risk of developing diabetes: a nested case-control study. Diabet. Med. 33, 631\u2013638 (2016).","journal-title":"Diabet. Med."},{"key":"4005_CR10","first-page":"368","volume":"46","author":"CH Jensen","year":"2019","unstructured":"Jensen, C. H. et al. The imprinted gene Delta like non-canonical notch ligand 1 (Dlk1) associates with obesity and triggers insulin resistance through inhibition of skeletal muscle glucose uptake. E-Bio Med. 46, 368\u2013380 (2019).","journal-title":"E-Bio Med."},{"key":"4005_CR11","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1111\/j.1365-2265.2008.03170.x","volume":"69","author":"C Hermida","year":"2008","unstructured":"Hermida, C. et al. The serum levels of the EGF\u2010like homeotic protein dlk1 correlate with different metabolic parameters in two hormonally different children populations in Spain. Clin. Endocrinol. 69, 216\u2013224 (2008).","journal-title":"Clin. Endocrinol."},{"key":"4005_CR12","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1033179","volume":"9","author":"S Palumbo","year":"2022","unstructured":"Palumbo, S. et al. Circulating levels of DLK1 and glucose homeostasis in girls with obesity: a pilot study. Front. Endocrinol. 9, 1033179 (2022).","journal-title":"Front. Endocrinol."},{"key":"4005_CR13","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1038\/ejhg.2008.64","volume":"16","author":"AK Wermter","year":"2008","unstructured":"Wermter, A. K. et al. Preferential reciprocal transfer of paternal\/maternal DLK1 alleles to obese children: first evidence of polar overdominance in humans. Eur. J. Hum. Genet. 16, 1126\u20131134 (2008).","journal-title":"Eur. J. Hum. Genet."},{"key":"4005_CR14","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/ng.3841","volume":"49","author":"FR Day","year":"2017","unstructured":"Day, F. R. et al. Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk. Nat. Genet. 49, 834\u2013841 (2017).","journal-title":"Nat. Genet."},{"key":"4005_CR15","doi-asserted-by":"publisher","first-page":"3165","DOI":"10.1210\/clinem\/dgaa461","volume":"105","author":"LR Montenegro","year":"2020","unstructured":"Montenegro, L. R. et al. Novel genetic and biochemical findings of DLK1 in children with central precocious puberty: a Brazilian\u2013Spanish Study. J. Clin. Endocrinol. Metab. 105, 3165\u20133172 (2020).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"4005_CR16","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0300-8932(99)74922-5","volume":"52","author":"F Rodr\u00edguez-Artalejo","year":"1999","unstructured":"Rodr\u00edguez-Artalejo, F. et al. Four provinces study: objectives and design. Rev. Esp. Cardiol. 52, 319\u2013326 (1999).","journal-title":"Rev. Esp. Cardiol."},{"key":"4005_CR17","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1136\/bmj.320.7244.1240","volume":"320","author":"TJ Cole","year":"2000","unstructured":"Cole, T. J., Bellizzi, M. C., Flegal, K. M. & Dietz, W. H. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 320, 1240\u20131243 (2000).","journal-title":"BMJ"},{"key":"4005_CR18","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1016\/j.jmb.2006.10.020","volume":"367","author":"ML Nueda","year":"2007","unstructured":"Nueda, M. L. et al. The novel gene EGFL9\/Dlk2, highly homologous to Dlk1, functions as a modulator of adipogenesis. J. Mol. Biol. 367, 1270\u20131280 (2007).","journal-title":"J. Mol. Biol."},{"key":"4005_CR19","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.cytogfr.2019.03.006","volume":"46","author":"G\u00c1 Traustad\u00f3ttir","year":"2019","unstructured":"Traustad\u00f3ttir, G. \u00c1. et al. The imprinted gene Delta like non-canonical Notch ligand 1 (Dlk1) is conserved in mammals, and serves a growth modulatory role during tissue development and regeneration through Notch dependent and independent mechanisms. Cytokine Growth Factor. Rev. 46, 17\u201327 (2019).","journal-title":"Cytokine Growth Factor. Rev."},{"key":"4005_CR20","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.bbalip.2009.12.006","volume":"1801","author":"S Virtue","year":"2010","unstructured":"Virtue, S. & Vidal-Puig, A. Adipose tissue expandability, lipotoxicity and the metabolic syndrome-an allostatic perspective. Biochim. Biophys. Acta 1801, 338\u2013349 (2010).","journal-title":"Biochim. Biophys. Acta"},{"key":"4005_CR21","doi-asserted-by":"crossref","unstructured":"White, U. Adipose tissue expansion in obesity, health, and disease. Front. Cell Dev. Biol. 11 (2023).","DOI":"10.3389\/fcell.2023.1188844"},{"key":"4005_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/sj.ijo.0802735","volume":"29","author":"DS Freedman","year":"2004","unstructured":"Freedman, D. S. et al. Relation of BMI to fat and fat-free mass among children and adolescents. Int. J. Obes. 29, 1\u20138 (2004).","journal-title":"Int. J. Obes."},{"key":"4005_CR23","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.cell.2021.12.016","volume":"185","author":"A Sakers","year":"2022","unstructured":"Sakers, A., De Siqueira, M. K., Seale, P. & Villanueva, C. J. Adipose-tissue plasticity in health and disease. Cell 185, 419\u2013446 (2022).","journal-title":"Cell"},{"key":"4005_CR24","first-page":"193","volume":"291","author":"V Baladr\u00f3n","year":"2002","unstructured":"Baladr\u00f3n, V. et al. The EGF-like homeotic protein dlk affects cell growth and interacts with growth-modulating molecules in the yeast two-hybrid system. BBRC 291, 193\u2013204 (2002).","journal-title":"BBRC"},{"key":"4005_CR25","doi-asserted-by":"crossref","unstructured":"D\u2019Aniello, F., et al. The role of DLK1 deficiency in central precocious puberty and association with metabolic dysregulation. Horm. Res. Paediatr, 1-11 (2024).","DOI":"10.1159\/000541554"},{"key":"4005_CR26","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1038\/nrg3766","volume":"15","author":"J Peters","year":"2014","unstructured":"Peters, J. The role of genomic imprinting in biology and disease: an expanding view. Nat. Rev. Genet. 15, 517\u2013530 (2014).","journal-title":"Nat. Rev. Genet."},{"key":"4005_CR27","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/414799a","volume":"414","author":"AR Saltiel","year":"2001","unstructured":"Saltiel, A. R. & Kahn, C. R. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414, 799\u2013806 (2001).","journal-title":"Nature"},{"key":"4005_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.106923","volume":"19","author":"Y Huang","year":"2023","unstructured":"Huang, Y. et al. A pref-1-controlled non-inflammatory mechanism of insulin resistance. iScience 19, 106923 (2023).","journal-title":"iScience"},{"key":"4005_CR29","doi-asserted-by":"publisher","first-page":"132","DOI":"10.3390\/ijms25010132","volume":"25","author":"X Lu","year":"2023","unstructured":"Lu, X. et al. Effects of adipose tissue-specific knockout of delta-like non-canonical notch ligand 1 on lipid metabolism in mice. Int. J. Mol. Sci. 25, 132 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"4005_CR30","doi-asserted-by":"crossref","unstructured":"Shi, Q., et al. Notch signaling pathway in cancer: from mechanistic insights to targeted therapies. Signal. Transduct. Target. Ther. 9 (2024).","DOI":"10.1038\/s41392-024-01828-x"},{"key":"4005_CR31","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.tem.2015.02.006","volume":"26","author":"P Bi","year":"2015","unstructured":"Bi, P. & Kuang, S. Notch signaling as a novel regulator of metabolism. Trends Endocrinol. Metab. 26, 248\u2013255 (2015).","journal-title":"Trends Endocrinol. Metab."},{"key":"4005_CR32","doi-asserted-by":"publisher","first-page":"32140","DOI":"10.1074\/jbc.M111.230110","volume":"286","author":"L Chen","year":"2011","unstructured":"Chen, L. et al. Delta-like 1\/Fetal antigen-1 (DLK1\/FA1) is a novel regulator of chondrogenic cell differentiation via inhibition of the AKT kinase-dependent pathway. J. Biol. Chem. 286, 32140\u201332149 (2011).","journal-title":"J. Biol. Chem."},{"key":"4005_CR33","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1038\/s12276-020-0430-0","volume":"52","author":"SH Lee","year":"2020","unstructured":"Lee, S. H., Lee, J. & Im, S. The cellular function of SCAP in metabolic signaling. Exp. Mol. Med. 52, 724\u2013729 (2020).","journal-title":"Exp. Mol. Med."},{"key":"4005_CR34","doi-asserted-by":"publisher","first-page":"114244","DOI":"10.1016\/j.biopha.2023.114244","volume":"159","author":"M Savova","year":"2023","unstructured":"Savova, M., Mihaylova, L., Tews, D., Wabitsch, M. & Georgiev, M. Targeting PI3K\/AKT signaling pathway in obesity. Biomed. Pharmacother. 159, 114244 (2023).","journal-title":"Biomed. Pharmacother."}],"container-title":["Pediatric Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04005-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04005-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04005-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T17:04:10Z","timestamp":1762880650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04005-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,21]]},"references-count":34,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["4005"],"URL":"https:\/\/doi.org\/10.1038\/s41390-025-04005-0","relation":{},"ISSN":["0031-3998","1530-0447"],"issn-type":[{"value":"0031-3998","type":"print"},{"value":"1530-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,21]]},"assertion":[{"value":"29 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 March 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 March 2025","order":4,"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":"Written informed consent to participate in this study was provided by the participant\u2019s legal guardian\/next of kin.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}