{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T03:49:27Z","timestamp":1788407367067,"version":"build-2803163510"},"reference-count":42,"publisher":"The Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T00:00:00Z","timestamp":1644278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020194","name":"Wellcome","doi-asserted-by":"publisher","award":["208363\/Z\/17\/Z"],"award-info":[{"award-number":["208363\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/501100020194","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020194","name":"Wellcome","doi-asserted-by":"publisher","award":["207462\/Z\/17\/Z"],"award-info":[{"award-number":["207462\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/501100020194","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020194","name":"Wellcome","doi-asserted-by":"publisher","award":["099038\/Z\/12\/Z"],"award-info":[{"award-number":["099038\/Z\/12\/Z"]}],"id":[{"id":"10.13039\/501100020194","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/15\/56\/31645"],"award-info":[{"award-number":["FS\/15\/56\/31645"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"name":"French National Agency of research"},{"name":"Direction g\u00e9n\u00e9rale de la Sant\u00e9"},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Genetic variants affecting the nuclear hormone receptor coactivator steroid receptor coactivator, SRC-1, have been identified in people with severe obesity and impair melanocortin signaling in cells and mice. As a result, obese patients with SRC-1 deficiency are being treated with a melanocortin 4 receptor agonist in clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Here, our aim was to comprehensively describe and characterize the clinical phenotype of SRC-1 variant carriers to facilitate diagnosis and clinical management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In genetic studies of 2462 people with severe obesity, we identified 23 rare heterozygous variants in SRC-1. We studied 29 adults and 18 children who were SRC-1 variant carriers and performed measurements of metabolic and endocrine function, liver imaging, and adipose tissue biopsies. Findings in adult SRC-1 variant carriers were compared to 30 age- and body mass index (BMI)-matched controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The clinical spectrum of SRC-1 variant carriers included increased food intake in children, normal basal metabolic rate, multiple fractures with minimal trauma (40%), persistent diarrhea, partial thyroid hormone resistance, and menorrhagia. Compared to age-, sex-, and BMI-matched controls, adult SRC-1 variant carriers had more severe adipose tissue fibrosis (46.2% vs 7.1% respectively, P\u2005=\u2005.03) and a suggestion of increased liver fibrosis (5\/13 cases vs 2\/13 in controls, odds ratio\u2005=\u20053.4), although this was not statistically significant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SRC-1 variant carriers exhibit hyperphagia in childhood, severe obesity, and clinical features of partial hormone resistance. The presence of adipose tissue fibrosis and hepatic fibrosis in young patients suggests that close monitoring for the early development of obesity-associated metabolic complications is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgac067","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T22:21:48Z","timestamp":1644358908000},"page":"e2532-e2544","source":"Crossref","is-referenced-by-count":22,"title":["Obesity Due to Steroid Receptor Coactivator-1 Deficiency Is Associated With Endocrine and Metabolic Abnormalities"],"prefix":"10.1210","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6646-5498","authenticated-orcid":false,"given":"Tessa M","family":"Cacciottolo","sequence":"first","affiliation":[{"name":"University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome-MRC Institute of Metabolic Science, Box 289, Addenbrooke\u2019s Hospital, Cambridge CB2 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