{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:47:53Z","timestamp":1791823673243,"version":"4.3.4"},"reference-count":0,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Obes Facts"],"abstract":"<jats:p>Introduction: Monogenetic obesity involving the POMC and MC4R pathway often result in severe obesity, Case presentation: Two sisters, both in their thirties, with a loss-of-function PCSK1 muta-tion and living with class III obesity (BMI\u2019s 42 kg\/m2 and 46 kg\/m2, respectively) was referred for obesity treatment. None of the women had obesity-related diseases; however, due to severe obesi-ty they were treated with semaglutide and tirzepatide resulting in weight loss between 16%-27% of initial body weight. Conclusion: Despite a loss-of-function PCSK1 mutation disrupting the POMC pathway, the two cases are suggestive of GLP-1RA efficacy both upstream and downstream POMC, illustrating a need for further investigations of the mechanism of action for GLP-1RA-based therapies.<\/jats:p>","DOI":"10.1159\/ofa\/adzag012","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:46:12Z","timestamp":1791459972000},"source":"Crossref","is-referenced-by-count":0,"title":["GLP-1RA based treatment in patients with a PCSK1 mutation has profound effects on body weight \u2013 two case reports"],"prefix":"10.1159","author":[{"given":"Trine Poder","family":"S\u00f8rensen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steen B\u00f8nl\u00f8kke","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens Meldgaard","family":"Bruun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid Bjerge","family":"Gribsholt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,10,12]]},"container-title":["Obesity Facts"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/ofa\/adzag012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:02:18Z","timestamp":1791820938000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/ofa\/adzag012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,12]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1159\/ofa\/adzag012","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.34308753","asserted-by":"subject"}]},"ISSN":["1662-4025","1662-4033"],"issn-type":[{"value":"1662-4025","type":"print"},{"value":"1662-4033","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,12]]}}}