{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:46:00Z","timestamp":1792075560162,"version":"4.4.0"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Forschung, Technologie und Raumfahrt","doi-asserted-by":"publisher","award":["01GL2407A"],"award-info":[{"award-number":["01GL2407A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Forschung, Technologie und Raumfahrt","doi-asserted-by":"publisher","award":["01GL2407A"],"award-info":[{"award-number":["01GL2407A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Cell Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Recent findings by Miller et al. (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"10.1056\/NEJMoa2512275\" ext-link-type=\"doi\">https:\/\/doi.org\/10.1056\/NEJMoa2512275<\/jats:ext-link>\n                    ) suggest a fundamental shift in the understanding of acquired hypothalamic obesity (aHO), proposing that this condition should be viewed as an \u03b1-melanocyte-stimulating hormone (\u03b1-MSH) deficiency syndrome. Building on these observations, we discuss the proposed underlying pathophysiological mechanisms and argue that aHO can be conceptualized as an injury-induced loss of melanocortin tone, analogous to an \u03b1-MSH deficiency. The marked clinical response to setmelanotide in affected individuals indicates that downstream melanocortin-4 receptor (MC4R)-dependent pathways remain functionally intact, supporting the concept of a hormone deficiency\u2013like state. We further explore the implications of this paradigm change, highlighting how this new framework may fundamentally change the diagnosis and management of patients with aHO.\n                  <\/jats:p>","DOI":"10.1186\/s40348-026-00260-1","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:08:26Z","timestamp":1792073306000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acquired hypothalamic obesity as \u03b1-MSH deficiency syndrome: a paradigm shift with therapeutic impact"],"prefix":"10.1186","volume":"13","author":[{"given":"Martin","family":"Wabitsch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Ulrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Denzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"issue":"1","key":"260_CR1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/S2213-8587(24)00283-3","volume":"13","author":"J Argente","year":"2025","unstructured":"Argente J et al (2025) Hypothalamic obesity: from basic mechanisms to clinical perspectives. Lancet Diabetes Endocrinol 13(1):57\u201368","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"2","key":"260_CR2","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1056\/NEJMoa2512275","volume":"395","author":"JL Miller","year":"2026","unstructured":"Miller JL et al (2026) Setmelanotide for the Treatment of Acquired Hypothalamic Obesity. N Engl J Med 395(2):138\u2013150","journal-title":"N Engl J Med"},{"issue":"7","key":"260_CR3","doi-asserted-by":"publisher","first-page":"3298","DOI":"10.1210\/jc.2003-031751","volume":"89","author":"HL M\u00fcller","year":"2004","unstructured":"M\u00fcller HL et al (2004) Longitudinal study on growth and body mass index before and after diagnosis of childhood craniopharyngioma. 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Lancet Diabetes Endocrinol 12(6):380\u2013389","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"3","key":"260_CR8","doi-asserted-by":"publisher","first-page":"567","DOI":"10.2337\/diabetes.55.03.06.db05-1143","volume":"55","author":"L Huo","year":"2006","unstructured":"Huo L, Grill HJ, Bj\u00f8rbaek C (2006) Divergent regulation of proopiomelanocortin neurons by leptin in the nucleus of the solitary tract and in the arcuate hypothalamic nucleus. Diabetes 55(3):567\u2013573","journal-title":"Diabetes"},{"issue":"1","key":"260_CR9","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1002\/cne.22221","volume":"518","author":"L Gautron","year":"2010","unstructured":"Gautron L, Lee C, Funahashi H, Friedman J, Lee S, Elmquist J (2010) Melanocortin-4 receptor expression in a vago-vagal circuitry involved in postprandial functions. J Comp Neurol 518(1):6\u201324","journal-title":"J Comp Neurol"},{"issue":"10","key":"260_CR10","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1016\/j.molmet.2016.07.009","volume":"5","author":"PJ Enriori","year":"2016","unstructured":"Enriori PJ et al (2016) \u03b1-Melanocyte stimulating hormone promotes muscle glucose uptake via melanocortin 5 receptors. Mol Metab 5(10):807\u2013822","journal-title":"Mol Metab"},{"issue":"1","key":"260_CR11","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1530\/EJE-11-0158","volume":"165","author":"HL M\u00fcller","year":"2011","unstructured":"M\u00fcller HL et al (2011) Post-operative hypothalamic lesions and obesity in childhood craniopharyngioma: results of the multinational prospective trial KRANIOPHARYNGEOM 2000 after 3-year follow-up. Eur J Endocrinol Jul 165(1):17\u201324","journal-title":"Eur J Endocrinol Jul"}],"container-title":["Molecular and Cellular Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40348-026-00260-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40348-026-00260-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40348-026-00260-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:08:27Z","timestamp":1792073307000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40348-026-00260-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,15]]},"references-count":11,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["260"],"URL":"https:\/\/doi.org\/10.1186\/s40348-026-00260-1","relation":{},"ISSN":["2194-7791"],"issn-type":[{"value":"2194-7791","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,15]]},"assertion":[{"value":"5 August 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"MW and CD served as Principal Investigators in the phase 3 clinical trial and have received honoraria from Rhythm for lectures and consulting\/advisory activities. MW is an Editorial Board member of Molecular and Cellular Pediatrics. MW was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"52"}}