{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:03:37Z","timestamp":1791407017077,"version":"4.3.3"},"reference-count":72,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6751","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2025,6,5]]},"abstract":"<jats:p>\n                    The melanocortin system centrally regulates energy homeostasis, with key components such as melanocortin-4 receptor (MC4R) and adenylyl cyclase 3 (ADCY3) in neuronal primary cilia. Mutations in\n                    <jats:italic toggle=\"yes\">MC4R<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">ADCY3<\/jats:italic>\n                    as well as ciliary dysfunction lead to obesity, but how melanocortin signaling works in cilia remains unclear. Using mouse random germline mutagenesis, we identified two missense mutations in\n                    <jats:italic toggle=\"yes\">G protein\u2013coupled receptor 45 (Gpr45)<\/jats:italic>\n                    that lead to obesity through hyperphagia. GPR45 was expressed in paraventricular nucleus of the hypothalamus (PVH), where it localized to cilia and recruited G\u03b1\n                    <jats:sub>s<\/jats:sub>\n                    to increase ciliary cyclic adenosine monophosphate (cAMP) via ADCY3. GPR45 colocalized with MC4R in PVH cilia and promoted ciliary MC4R activation. Loss of GPR45 in the PVH or MC4R\n                    <jats:sup>+<\/jats:sup>\n                    neurons caused obesity. These findings establish GPR45 as a key regulator of the ciliary melanocortin system, bridging MC4R and ADCY3.\n                  <\/jats:p>","DOI":"10.1126\/science.adp3989","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T17:07:24Z","timestamp":1749143244000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":26,"title":["GPR45 modulates G\u03b1\n                    <sub>s<\/sub>\n                    at primary cilia of the paraventricular hypothalamus to control food intake"],"prefix":"10.1126","volume":"388","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5546-8984","authenticated-orcid":true,"given":"Yu","family":"Xun","sequence":"first","affiliation":[{"name":"Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, USA."},{"name":"Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA."},{"name":"Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8236-4868","authenticated-orcid":true,"given":"Yiao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, USA."},{"name":"Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7853-1213","authenticated-orcid":true,"given":"Baijie","family":"Xu","sequence":"additional","affiliation":[{"name":"The Hypothalamic Research Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 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Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4790-3090","authenticated-orcid":true,"given":"Saikat","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5922-0951","authenticated-orcid":true,"given":"Chen","family":"Liu","sequence":"additional","affiliation":[{"name":"The Hypothalamic Research Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA."},{"name":"Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA."},{"name":"Peter O\u2019Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, 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