{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T11:50:43Z","timestamp":1775994643101,"version":"3.50.1"},"posted":{"date-parts":[[2025,6,17]]},"group-title":"Physiology","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,17]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Human thermogenesis depends on \u03b22-adrenoceptors (\u03b22AR) expressed in thermogenic adipocytes, which are activated by norepinephrine released from sympathetic neurons. Whether \u03b22AR also modulates thermogenesis via direct presynaptic action within sympathetic neurons has remained unclear. Here, we identify\n                  <jats:italic>Adrb2<\/jats:italic>\n                  expression in human and rodent cervical sympathetic neurons. \u03b22AR agonism exerts neurotrophic effects and facilitates cholinergic responsiveness in mouse sympathetic neurons, indicating a\n                  <jats:italic>sympathofacilitatory<\/jats:italic>\n                  role. Selective deletion of \u03b22AR in sympathetic neurons leads to impaired nerve activity in brown adipose tissue, sympathetic neuropathy, worsened fasting-induced hypothermia, and progressive obesity in chow-fed mice\u2014without changes in food intake. These findings uncover a presynaptic role for \u03b22AR in sustaining thermogenesis and regulating adiposity, suggesting\n                  <jats:italic>sympathofacilitation as<\/jats:italic>\n                  a therapeutic avenue for obesity.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>\n                        Human and mouse cervical sympathetic neurons express\n                        <jats:italic>adrenoceptor beta 2<\/jats:italic>\n                        (\n                        <jats:italic>Adrb2<\/jats:italic>\n                        )\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\u03b22-adrenoceptor (\u03b22AR) activation is neurotrophic and facilitates sympathetic neuronal excitability<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Loss of \u03b22AR in sympathetic neurons leads to neuropathy in brown adipose tissue and reduced sympathetic activity<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Deletion of \u03b22AR in sympathetic neurons exacerbates fasting-induced hypothermia and promotes obesity independently of food intake<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2025.06.13.659468","type":"posted-content","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T03:20:17Z","timestamp":1750216817000},"source":"Crossref","is-referenced-by-count":0,"title":["\u0392\n                  <sub>2<\/sub>\n                  AR Agonists Sustain Thermogenesis and Leanness via\n                  <i>Sympathofacilitation<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8124-569X","authenticated-orcid":false,"given":"Samson W.","family":"Cheung","sequence":"first","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Sidarta-Oliveira","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yitao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gitalee","family":"Sarker","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Lundh","sequence":"additional","affiliation":[{"name":"Department of Pathology and Imaging, Global Drug Discovery, Novo Nordisk A\/S, M\u00e5l\u00f8v, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald A.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, and Veterans Affairs Health Care System, Iowa City, IA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sian","family":"Wilcox","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK"},{"name":"Sleep and Circadian Neuroscience Institute, University of Oxford, Sherrington Rd, Oxford OX1 3QU, UK"},{"name":"The Kavli Institute for Nanoscience Discovery, University of Oxford, Sherrington Rd, Oxford OX1 3QU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladyslav","family":"Vyazovskiy","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK"},{"name":"Sleep and Circadian Neuroscience Institute, University of Oxford, Sherrington Rd, Oxford OX1 3QU, UK"},{"name":"The Kavli Institute for Nanoscience Discovery, University of Oxford, Sherrington Rd, Oxford OX1 3QU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Paterson","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamal","family":"Rahmouni","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology, Roy J. and Lucille A. 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