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Obese, diabetic (ob\/ob) mice treated with five doses of ENT\u201003 over 2\u2009weeks, demonstrated a rapid decrease in blood glucose levels into the range seen in non\u2010obese animals, prior to any significant weight loss. Weight fell substantially thereafter as food intake decreased, and serum biochemical parameters normalized compared with both vehicle and pair\u2010fed controls. To determine whether ENT\u201003 could be acting centrally, we injected a single dose of ENT\u201003 intracerebroventricularly to Sprague\u2013Dawley rats. Weight fell significantly and remained below vehicle injected controls for an extended period. By autoradiography, ENT\u201003 localized to the arcuate nucleus of the hypothalamus, the choroid plexus and cerebrospinal fluid. Significant cFos\u00a0activation occurred in multiple anatomical regions within the hypothalamus and brainstem involved in appetite suppression, food\u2010entrained circadian rhythmicity, autonomic function, and growth. These data support a role for ENT\u201003 in the treatment of type 2 diabetes and obesity. Phase 1 studies in subjects with obesity and diabetes are currently in progress.<\/jats:p>","DOI":"10.1111\/dom.15940","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T00:05:01Z","timestamp":1727049901000},"page":"5701-5712","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A novel, centrally acting mammalian aminosterol,\n                    <scp>ENT<\/scp>\n                    \u201003, induces weight loss in obese and lean rodents"],"prefix":"10.1111","volume":"26","author":[{"given":"Denise","family":"Barbut","sequence":"first","affiliation":[{"name":"Enterin, Inc.  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