{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:38:00Z","timestamp":1773009480807,"version":"3.50.1"},"reference-count":67,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To evaluate the therapeutic potential of leptin treatment for weight loss maintenance preclinically, through a systematic evaluation of leptin efficacy (a) following a period of weight loss stability (as in published clinical studies), and (b) across a range of circulating leptin concentrations achieved through a variety of different weight loss conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials\/Methods<\/jats:title>\n                    <jats:p>Body weight and plasma leptin reduction were achieved via caloric restriction in diet\u2010induced obese (DIO) male mice. The effect of r\u2010Leptin (pulsatile exposure) or Fc\u2010Leptin (continuous exposure), administered centrally or systemically, on the prevention of weight regain was tested in a variety of conditions aimed at lowering circulating leptin levels: following 10% or 20% weight loss, with or without a prior weight loss stabilization period, or dietary fat reduction from 60% to 30%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Leptin treatment (physiological to pharmacological dose ranges) did not prevent weight regain in the 10% weight loss (30% leptin lowering) model with or without a weight loss stabilization period. In contrast, liraglutide was effective in maintaining weight loss. Continuous high CNS leptin exposure targeting up to 35\u2009nM (585\u2009ng\/mL) in CSF via intracerebroventricular infusion maintained weight loss in non\u2010obese chow\u2010fed mice but was ineffective in DIO mice. Lowering circulating leptin to non\u2010obese mouse concentrations via either achieving greater weight loss (20%) or reducing dietary fat content (60% to 30%) was also not sufficient to reveal a leptin benefit on weight regain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Leptin treatment is not sufficient to maintain caloric restriction\u2010induced weight loss in preclinical models and does not support the theory that leptin resistance in obesity is due to excessive leptin production and saturation of leptin signalling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70207","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T09:35:03Z","timestamp":1760693703000},"page":"401-416","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of leptin treatment on maintenance of body weight loss in diet\u2010induced obese mice"],"prefix":"10.1111","volume":"28","author":[{"given":"Danna M.","family":"Breen","sequence":"first","affiliation":[{"name":"Internal Medicine Research Unit, Pfizer Research &amp; Development  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3332-3597","authenticated-orcid":false,"given":"Roc\u00edo M.","family":"Saavedra\u2010Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Internal Medicine Research Unit, Pfizer Research &amp; Development  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Joaquim","sequence":"additional","affiliation":[{"name":"Internal Medicine Research Unit, Pfizer Research &amp; Development  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jimmy","family":"Kong","sequence":"additional","affiliation":[{"name":"Internal Medicine Research Unit, Pfizer Research &amp; Development  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Reese","sequence":"additional","affiliation":[{"name":"Internal Medicine Research Unit, Pfizer Research &amp; Development  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9240-4867","authenticated-orcid":false,"given":"J. 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