{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:01:45Z","timestamp":1785402105489,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,29]]},"group-title":"Physiology","reference-count":53,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["DK143978"],"award-info":[{"award-number":["DK143978"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DK104789"],"award-info":[{"award-number":["DK104789"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DK143978"],"award-info":[{"award-number":["DK143978"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DK123075"],"award-info":[{"award-number":["DK123075"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DK125353"],"award-info":[{"award-number":["DK125353"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DK046492"],"award-info":[{"award-number":["DK046492"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DK137791"],"award-info":[{"award-number":["DK137791"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DK020579"],"award-info":[{"award-number":["DK020579"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DK124723"],"award-info":[{"award-number":["DK124723"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1-25-PDF-121"],"award-info":[{"award-number":["1-25-PDF-121"]}],"id":[{"id":"https:\/\/ror.org\/04f6cgz95","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["19CDA34670007"],"award-info":[{"award-number":["19CDA34670007"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Pathologic white adipose tissue (WAT) remodeling, characterized by fibrosis, inflammation, and adipocyte dysfunction, is a hallmark and driver of metabolic disease in obesity\n                  <jats:sup>1<\/jats:sup>\n                  . Here, we show that legacy effects of early physiological or pharmacological interventions driving adaptive adipose remodeling can mitigate maladaptive WAT remodeling and metabolic dysfunction when developing obesity later in life. Cold exposure or \u03b23-adrenergic receptor (\u03b23AR) agonism (CL316,243) induced thermogenic remodeling of WAT in male mice. After a prolonged recovery at room temperature, trained epididymal WAT reverted to an energy-storing state but retained a population of adipocytes resembling \u201cmetabolically flexible\u201d visceral adipocytes found in human metabolically healthy obesity. The legacy of the antecedent treatment conferred lasting protection against glucose intolerance when later developing high fat diet (HFD)-induced obesity, with insulin sensitivity persisting for at least 20 weeks of overnutrition. This metabolic resilience was accompanied by healthy epididymal WAT expansion with reduced fibrosis and inflammation. Our findings demonstrate that short-term interventions, without genetic manipulation, can \u201ctrain\u201d adipose tissue, enhancing its long-term plasticity and conferring durable protection against future obesity-associated insulin resistance.\n                <\/jats:p>","DOI":"10.64898\/2026.06.23.734002","type":"posted-content","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T01:15:23Z","timestamp":1782782123000},"source":"Crossref","is-referenced-by-count":0,"title":["Legacy Effects of Early \u03b2-Adrenergic Stimulation Program Adipose Plasticity and Confer Metabolic Resilience in Obesity"],"prefix":"10.64898","author":[{"given":"Pablo E.","family":"Morales","sequence":"first","affiliation":[{"name":"Duke Molecular Physiology Institute, Division of Endocrinology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Tong","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Division of Endocrinology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavanya","family":"Vishvanath","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Division of Endocrinology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle C.","family":"Leander","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Division of Endocrinology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor E.","family":"Wade","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Division of Endocrinology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Hallaron","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Division of Endocrinology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberley","family":"El","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Division of Endocrinology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Hollander","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Division of Endocrinology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Truong","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Division of Endocrinology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Wothe","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Division of Endocrinology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Elmquist","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Touchstone Diabetes Center, University of Texas Southwestern Medical Center; Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjori","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Department of Internal Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather K.","family":"Hamilos","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Center, Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace E.","family":"Dewyer","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Center, Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clair","family":"Crewe","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Department of Internal Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William L.","family":"Holland","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Center, Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.","family":"Koves","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Division of Endocrinology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah M.","family":"Muoio","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Division of Endocrinology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"D\u2019Alessio","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Division of Endocrinology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Cannavino","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Division of Endocrinology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan E.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Division of Endocrinology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengle","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Touchstone Diabetes Center, University of Texas Southwestern Medical Center; Dallas, TX, USA"},{"name":"State Key Laboratory of Immune Response and Immunotherapy, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 200031, China. (Current address)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana K.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Division of Endocrinology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA"},{"name":"Department of Internal Medicine, Touchstone Diabetes Center, University of Texas Southwestern Medical Center; Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070205053194000_2026.06.23.734002v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.12.016"},{"key":"2026070205053194000_2026.06.23.734002v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.03.002"},{"key":"2026070205053194000_2026.06.23.734002v1.3","doi-asserted-by":"publisher","DOI":"10.1172\/JCI129186"},{"key":"2026070205053194000_2026.06.23.734002v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.10.010"},{"key":"2026070205053194000_2026.06.23.734002v1.5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00586.2009"},{"key":"2026070205053194000_2026.06.23.734002v1.6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI129191"},{"key":"2026070205053194000_2026.06.23.734002v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03196-x"},{"key":"2026070205053194000_2026.06.23.734002v1.8","doi-asserted-by":"publisher","DOI":"10.1172\/JCI88883"},{"key":"2026070205053194000_2026.06.23.734002v1.9","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0585"},{"key":"2026070205053194000_2026.06.23.734002v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-022-00613-w"},{"key":"2026070205053194000_2026.06.23.734002v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00350-0"},{"key":"2026070205053194000_2026.06.23.734002v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.11.002"},{"key":"2026070205053194000_2026.06.23.734002v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(94)00408-0"},{"key":"2026070205053194000_2026.06.23.734002v1.14","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1998.274.5.R1212"},{"key":"2026070205053194000_2026.06.23.734002v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2740"},{"key":"2026070205053194000_2026.06.23.734002v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.03.005"},{"key":"2026070205053194000_2026.06.23.734002v1.17","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0308"},{"key":"2026070205053194000_2026.06.23.734002v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.05.011"},{"key":"2026070205053194000_2026.06.23.734002v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37386-z"},{"key":"2026070205053194000_2026.06.23.734002v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.054"},{"key":"2026070205053194000_2026.06.23.734002v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01479-0"},{"key":"2026070205053194000_2026.06.23.734002v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.12.004"},{"key":"2026070205053194000_2026.06.23.734002v1.23","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"2026070205053194000_2026.06.23.734002v1.24","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01300-08"},{"key":"2026070205053194000_2026.06.23.734002v1.25","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-0761"},{"key":"2026070205053194000_2026.06.23.734002v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.12.008"},{"key":"2026070205053194000_2026.06.23.734002v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.10.018"},{"key":"2026070205053194000_2026.06.23.734002v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.11.006"},{"key":"2026070205053194000_2026.06.23.734002v1.29","doi-asserted-by":"publisher","DOI":"10.1101\/2025.09.14.673351"},{"key":"2026070205053194000_2026.06.23.734002v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ihj.2018.12.001"},{"key":"2026070205053194000_2026.06.23.734002v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00893-w"},{"key":"2026070205053194000_2026.06.23.734002v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0102-y"},{"key":"2026070205053194000_2026.06.23.734002v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/s41366-023-01270-z"},{"key":"2026070205053194000_2026.06.23.734002v1.34","doi-asserted-by":"publisher","DOI":"10.1172\/JCI131126"},{"key":"2026070205053194000_2026.06.23.734002v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/srep30409"},{"key":"2026070205053194000_2026.06.23.734002v1.36","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00452"},{"key":"2026070205053194000_2026.06.23.734002v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.05.012"},{"key":"2026070205053194000_2026.06.23.734002v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.03.012"},{"key":"2026070205053194000_2026.06.23.734002v1.39","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.27669"},{"key":"2026070205053194000_2026.06.23.734002v1.40","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44271"},{"key":"2026070205053194000_2026.06.23.734002v1.41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.491936"},{"key":"2026070205053194000_2026.06.23.734002v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.03.032"},{"key":"2026070205053194000_2026.06.23.734002v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2015.02.004"},{"key":"2026070205053194000_2026.06.23.734002v1.44","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-022-00667-w"},{"key":"2026070205053194000_2026.06.23.734002v1.45","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2026070205053194000_2026.06.23.734002v1.46","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"2026070205053194000_2026.06.23.734002v1.47","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2026070205053194000_2026.06.23.734002v1.48","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.97981"},{"key":"2026070205053194000_2026.06.23.734002v1.49","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34681-z"},{"key":"2026070205053194000_2026.06.23.734002v1.50","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giaa151"},{"key":"2026070205053194000_2026.06.23.734002v1.51","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01767-y"},{"key":"2026070205053194000_2026.06.23.734002v1.52","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv711"},{"key":"2026070205053194000_2026.06.23.734002v1.53","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.06.23.734002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T12:06:23Z","timestamp":1782993983000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.06.23.734002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,29]]},"references-count":53,"URL":"https:\/\/doi.org\/10.64898\/2026.06.23.734002","relation":{},"subject":[],"published":{"date-parts":[[2026,6,29]]},"subtype":"preprint"}}