{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:59:39Z","timestamp":1785308379355,"version":"3.55.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    Primary cilia are specialized signaling organelles that concentrate selected G protein-coupled receptors and are important in neuronal and metabolic regulation. Neuropeptide Y receptor 2 (NPY2R), a receptor implicated in feeding and energy homeostasis, localizes to neuronal primary cilia in the hypothalamus. Although fasting-associated shortening of NPY2R-positive cilia in the arcuate nucleus (ARC) has recently been reported, it remains unclear whether this response reflects direct, ligand-driven structural remodeling of NPY2R-positive cilia, whether distinct nutritional states differentially regulate this receptor-defined ciliary compartment across feeding-related brain regions, and which intracellular mechanisms mediate these changes. Here, we show that neuropeptide Y (NPY) directly induces structural retraction of NPY2R-positive primary cilia, that nutritional states differentially remodel this receptor-defined ciliary compartment in a region-specific manner, and that NPY-driven ciliary retraction is mediated by Gi\/o-dependent Akt\/JNK signaling.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , fasting shortened NPY2R-positive primary cilia in two of five examined regions, the ARC and ventromedial hypothalamus, whereas the adenylyl cyclase 3 (AC3)-positive ciliary population remained unchanged. Conversely, chronic high-fat diet feeding induced a distinct, region-dependent remodeling pattern in both NPY2R-positive and AC3-positive cilia.\n                    <jats:italic>Ex vivo<\/jats:italic>\n                    , direct NPY stimulation shortens endogenous NPY2R-positive primary cilia in hypothalamic slice cultures.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , using a reconstituted human retinal pigment epithelial cell model expressing ciliary NPY2R, we found that this structural retraction was time-dependent, highly ligand-sensitive, reversible, and mediated by Gi\/o-dependent Akt\/JNK signaling. Notably, NPY-induced ciliary shortening and the reduction in NPY2R-positive cilia-bearing cells showed different sensitivities to Akt\/JNK inhibition. Collectively, these findings demonstrate that NPY can directly remodel endogenous receptor-defined primary cilia and suggest that the ligand-driven structural plasticity of NPY2R-positive cilia may contribute to the tuning of hypothalamic signaling in response to changing nutritional conditions.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2026.1909565","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:02:37Z","timestamp":1785304957000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic regulation of hypothalamic NPY2R-positive primary cilia by nutritional states"],"prefix":"10.3389","volume":"14","author":[{"given":"Akie","family":"Hamamoto","sequence":"first","affiliation":[{"name":"Graduate School of Integrated Sciences for Life, Hiroshima University","place":["Hiroshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuya","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Graduate School of Integrated Sciences for Life, Hiroshima University","place":["Hiroshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumiko","family":"Saito","sequence":"additional","affiliation":[{"name":"Graduate School of Integrated Sciences for Life, Hiroshima University","place":["Hiroshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Graduate School of Integrated Sciences for Life, Hiroshima University","place":["Hiroshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e0170756","DOI":"10.1371\/journal.pone.0170756","article-title":"Adenylate cyclase type III is not a ubiquitous marker for all primary cilia during development","volume":"12","author":"Antal","year":"2017","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/s41581-019-0116-9","article-title":"Cellular signalling by primary cilia in development, organ function and disease","volume":"15","author":"Anvarian","year":"2019","journal-title":"Nat. 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