{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:56:55Z","timestamp":1793296615635,"version":"4.5.0"},"reference-count":41,"publisher":"American Society for Clinical Investigation","issue":"2","funder":[{"name":"NIH","award":["NIH U54 HD 090216"],"award-info":[{"award-number":["NIH U54 HD 090216"]}]},{"name":"NIH NIDDK","award":["103033"],"award-info":[{"award-number":["103033"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,30]]},"abstract":"<jats:p>\n                    The ciliopathies Bardet-Biedl syndrome and Alstr\u00f6m syndrome are genetically inherited pleiotropic disorders with hyperphagia and obesity as primary clinical features. Methionine aminopeptidase 2 inhibitors (MetAP2i) have been shown in preclinical and clinical studies to reduce food intake, body weight, and adiposity. Here, we investigated the effects of MetAP2i administration in a mouse model of ciliopathy produced by conditional deletion of the\n                    <jats:italic>Thm1<\/jats:italic>\n                    gene in adulthood.\n                    <jats:italic>Thm1<\/jats:italic>\n                    conditional knockout (cko) mice showed decreased hypothalamic proopiomelanocortin expression as well as hyperphagia, obesity, metabolic disease, and hepatic steatosis. In obese\n                    <jats:italic>Thm1<\/jats:italic>\n                    -cko mice, 2-week administration of MetAP2i reduced daily food intake and reduced body weight 17.1% from baseline (vs. 5% reduction for vehicle). This was accompanied by decreased levels of blood glucose, insulin, and leptin. Further, MetAP2i reduced gonadal adipose depots and adipocyte size and improved liver morphology. This is the first report to our knowledge of MetAP2i reducing hyperphagia and body weight and ameliorating metabolic indices in a mouse model of ciliopathy. These results support further investigation of MetAP2 inhibition as a potential therapeutic strategy for ciliary-mediated forms of obesity.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.134278","type":"journal-article","created":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T12:02:36Z","timestamp":1577361756000},"source":"Crossref","is-referenced-by-count":11,"title":["MetAP2 inhibition reduces food intake and body weight in a ciliopathy mouse model of obesity"],"prefix":"10.1172","volume":"5","author":[{"given":"Tana S.","family":"Pottorf","sequence":"first","affiliation":[{"name":"Jared Grantham Kidney Institute and"},{"name":"Department of Anatomy and Cell Biology, University of Kansas Medical Center (KUMC), Kansas City, Kansas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micaella P.","family":"Fagan","sequence":"additional","affiliation":[{"name":"Zafgen Inc., Boston, Massachusetts, 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