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Hillblom Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001167","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Primary cilia are sensory cellular appendages that regulate diverse developmental and homeostatic processes, including energy homeostasis. In animal models and humans, their dysfunction can lead to hyperphagia and obesity. ARL13B is a regulatory GTPase enriched in cilia. We engineered an Arl13b mouse allele, Arl13bV358A, that disrupts ARL13B from localizing to primary cilia. Homozygous Arl13bV358A\/V358A mice become hyperphagic, obese, and insulin-resistant. Restoring wild-type ARL13B to cilia in 4-week-old Arl13bV358A\/V358A mice fully rescued the obesity and metabolic dysfunction. Additionally, the selective exclusion of ARL13B from cilia in the nervous system caused obesity. Together, these findings establish that ciliary ARL13B function within the nervous system is necessary for body weight regulation. Our ability to genetically uncouple the ciliary and nonciliary functions of ARL13B in a cell-type\u2013specific manner enables us to define its cilia-specific role and offers new insights into the molecular mechanisms underlying primary cilia control of energy homeostasis.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>The molecular mechanisms by which primary cilia regulate energy homeostasis remain poorly understood. Here, we evaluated whether the ciliary GTPase ARL13B regulates energy homeostasis and whether its localization to cilia is required to control body weight and feeding. Using genetic tools to isolate cilia-specific functions, we found that systemic exclusion of ARL13B from cilia causes hyperphagia and obesity in mice and that ciliary ARL13B is required in the nervous system for weight control. These findings identify ciliary ARL13B as a key regulator of energy homeostasis, contributing to our understanding of how primary cilia act as metabolic signaling hubs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-1099","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T18:35:01Z","timestamp":1785350101000},"update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["Ciliary ARL13B Is Essential for Body Weight Regulation in Mice"],"prefix":"10.2337","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2729-6281","authenticated-orcid":false,"given":"Tiffany T.","family":"Terry","sequence":"first","affiliation":[{"name":"1Department of Human Genetics, Emory University School of Medicine, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1486-5377","authenticated-orcid":false,"given":"Eduardo D.","family":"Gigante","sequence":"additional","affiliation":[{"name":"1Department of Human Genetics, Emory University School of Medicine, Atlanta, GA"},{"name":"2Graduate Program in Neuroscience, Laney Graduate School, Emory University, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2978-2648","authenticated-orcid":false,"given":"Coralie M.","family":"Alexandre","sequence":"additional","affiliation":[{"name":"3Diabetes Center and Department of Medicine, University of California, San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3498-4492","authenticated-orcid":false,"given":"Kathryn M.","family":"Brewer","sequence":"additional","affiliation":[{"name":"4Department of Biology, Indiana University-Indianapolis, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6187-5906","authenticated-orcid":false,"given":"Xinyu","family":"Yue","sequence":"additional","affiliation":[{"name":"3Diabetes Center and Department of Medicine, University of California, San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2863-1069","authenticated-orcid":false,"given":"Nicolas F.","family":"Berbari","sequence":"additional","affiliation":[{"name":"4Department of Biology, Indiana University-Indianapolis, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4274-7033","authenticated-orcid":false,"given":"Christian","family":"Vaisse","sequence":"additional","affiliation":[{"name":"3Diabetes Center and Department of Medicine, University of California, San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6579-7589","authenticated-orcid":false,"given":"Tamara","family":"Caspary","sequence":"additional","affiliation":[{"name":"1Department of Human Genetics, Emory University School of Medicine, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2026,7,29]]},"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/doi\/10.2337\/db25-1099\/889521\/db251099.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/doi\/10.2337\/db25-1099\/889521\/db251099.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T18:35:02Z","timestamp":1785350102000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/doi\/10.2337\/db25-1099\/172251\/Ciliary-ARL13B-Is-Essential-for-Body-Weight"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,29]]},"references-count":0,"URL":"https:\/\/doi.org\/10.2337\/db25-1099","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,29]]},"article-number":"db251099"}}