{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:42:10Z","timestamp":1791042130463,"version":"4.1.0"},"reference-count":32,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The present studies aimed to identify mechanisms contributing to amylin\/leptin synergy in reducing body weight and adiposity. We reasoned that if amylin\/leptin harnessed complementary neuronal pathways, then in the leptin-sensitive state, amylin should augment leptin signaling\/binding and that in the absence of endogenous amylin, leptin signaling should be diminished. Amylin (50 \u03bcg\/kg, ip) amplified low-dose leptin-stimulated (15 \u03bcg\/kg, ip) phosphorylated signal transducer and activator of transcription-3 signaling within the arcuate nucleus (ARC) in lean rats. Amylin (50 \u03bcg\/kg \u00b7 d) or leptin (125 \u03bcg\/kg \u00b7 d) infusion to lean rats decreased 28-d food intake (14 and 10%, respectively), body weight (amylin by 4.3%, leptin by 4.9%), and epididymal fat (amylin by 19%, leptin by 37%). Amylin\/leptin co-infusion additively decreased food intake (by 26%) and reduced body weight (by 15%) and epididymal fat (by 78%; all P &amp;lt; 0.05 vs. all groups) in a greater than mathematically additive manner, consistent with synergy. Amylin increased leptin binding within the ventromedial hypothalamus (VMN) by 35% and dorsomedial hypothalamus by 47% (both P &amp;lt; 0.05 vs. vehicle). Amylin\/leptin similarly increased leptin binding in the VMN by 40% and ARC by 70% (P &amp;lt; 0.05 vs. vehicle). In amylin-deficient mice, hypothalamic leptin receptor mRNA expression was reduced by 50%, leptin-stimulated phosphorylated signal transducer and activator of transcription-3 within ARC and VMN was reduced by 40%, and responsiveness to leptin\u2019s (1 mg\/kg \u00b7 d for 28 d) weight-reducing effects was attenuated (all P &amp;lt; 0.05 vs. wild-type controls). We suggest that amylin\/leptin\u2019s marked weight- and fat-reducing effects are due to activation of intrinsic synergistic neuronal signaling pathways and further point to the integrated neurohormonal therapeutic potential of amylin\/leptin agonism in obesity.<\/jats:p>","DOI":"10.1210\/en.2009-0546","type":"journal-article","created":{"date-parts":[[2009,10,30]],"date-time":"2009-10-30T02:14:56Z","timestamp":1256868896000},"page":"143-152","source":"Crossref","is-referenced-by-count":133,"title":["Mechanisms of Amylin\/Leptin Synergy in Rodent Models"],"prefix":"10.1210","volume":"151","author":[{"given":"Victoria F.","family":"Turek","sequence":"first","affiliation":[{"name":"Amylin Pharmaceuticals (V.F.T., J.L.T., G.G., C.W., P.S.G., C.V., D.G.P., J.D.R.), San Diego, California 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Trevaskis","sequence":"first","affiliation":[{"name":"Amylin Pharmaceuticals (V.F.T., J.L.T., G.G., C.W., P.S.G., C.V., D.G.P., J.D.R.), San Diego, California 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry E.","family":"Levin","sequence":"first","affiliation":[{"name":"Neurology Service (B.E.L., A.A.D.-M., B.I.), Veterans Affairs Medical Center, East Orange, New Jersey 07018"},{"name":"Department of Neurology and Neurosciences (B.E.L., A.A.D.-M., B.I.), New Jersey Medical School, Newark, New Jersey 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambrose A.","family":"Dunn-Meynell","sequence":"first","affiliation":[{"name":"Neurology Service (B.E.L., A.A.D.-M., B.I.), Veterans Affairs Medical Center, East Orange, New Jersey 07018"},{"name":"Department of Neurology and Neurosciences (B.E.L., A.A.D.-M., B.I.), New Jersey Medical School, Newark, New Jersey 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boman","family":"Irani","sequence":"first","affiliation":[{"name":"Neurology Service (B.E.L., A.A.D.-M., B.I.), Veterans 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92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin","family":"Vu","sequence":"first","affiliation":[{"name":"Amylin Pharmaceuticals (V.F.T., J.L.T., G.G., C.W., P.S.G., C.V., D.G.P., J.D.R.), San Diego, California 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Parkes","sequence":"first","affiliation":[{"name":"Amylin Pharmaceuticals (V.F.T., J.L.T., G.G., C.W., P.S.G., C.V., D.G.P., J.D.R.), San Diego, California 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Roth","sequence":"first","affiliation":[{"name":"Amylin Pharmaceuticals (V.F.T., J.L.T., G.G., C.W., P.S.G., C.V., D.G.P., J.D.R.), San Diego, California 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613104774200_R1","doi-asserted-by":"crossref","first-page":"7257","DOI":"10.1073\/pnas.0706473105","article-title":"Leptin responsiveness restored by amylin 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