{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:47:50Z","timestamp":1792626470522,"version":"4.5.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD034209 , 1R01DK141613 , 5R01DK137798, P20GM121301 , U54GM115516"],"award-info":[{"award-number":["S10OD034209 , 1R01DK141613 , 5R01DK137798, P20GM121301 , U54GM115516"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Beyond its primary digestive functions, the stomach serves as an endocrine organ, secreting peptides that regulate appetite and energy balance. Among its enteroendocrine populations, X\/A-like cells play a pivotal role in controlling food intake, glucose homeostasis, and lipid deposition. The secretion of X\/A-like cell-derived hormones, including ghrelin and nesfatin-1, is regulated by the mechanistic target of rapamycin (mTOR) signaling pathway. However, the role of X\/A-like cell mTOR signaling in skeletal metabolism remains unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      Using previously validated and published mouse models with X\/A-like cell-specific deletion of\n                      <jats:italic>Mtor<\/jats:italic>\n                      or its upstream inhibitor\n                      <jats:italic>Tsc1<\/jats:italic>\n                      , we assessed bone phenotypes at 12 and 40 weeks of age under chow-fed conditions. Skeletal effects were also evaluated under pathological bone loss conditions, including estrogen deficiency (ovariectomy) and caloric restriction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our findings demonstrate that mTOR signaling deficiency in X\/A-like cells compromises bone health in male mice, evidenced by cortical bone loss at 12 weeks and trabecular bone reductions at 40 weeks. Furthermore, X\/A-like cell-specific\n                      <jats:italic>Mtor<\/jats:italic>\n                      deletion significantly exacerbated bone loss in female mice following ovariectomy, impacting both trabecular and cortical parameters. In contrast, activation of mTOR signaling via\n                      <jats:italic>Tsc1<\/jats:italic>\n                      deletion in X\/A-like cells did not alter bone mass under either chow\n                      <jats:italic>ad libitum<\/jats:italic>\n                      or calorie-restricted conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Collectively, these findings identify a previously unrecognized role of gastric X\/A-like cell mTOR signaling in the regulation of bone metabolism. Maintenance of intact mTOR signaling in these endocrine cells is necessary for bone homeostasis, revealing a novel gut\u2013bone endocrine axis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1763507","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:06:44Z","timestamp":1775801204000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Intact mTOR signaling in gastric X\/A-like cells is required for bone homeostasis"],"prefix":"10.3389","volume":"17","author":[{"given":"Tiange","family":"Feng","sequence":"first","affiliation":[{"name":"Center for Molecular Medicine, MaineHealth Institute for Research","place":["Scarborough, ME, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhen","family":"Yin","sequence":"additional","affiliation":[{"name":"Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline C.","family":"Picoli","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, MaineHealth Institute for Research","place":["Scarborough, ME, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, MaineHealth Institute for Research","place":["Scarborough, ME, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuong T.","family":"Le","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, MaineHealth Institute for Research","place":["Scarborough, ME, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Liu","sequence":"additional","affiliation":[{"name":"University of New England, College of Osteopathic Medicine","place":["Biddeford, ME, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruili","family":"Yu","sequence":"additional","affiliation":[{"name":"Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May","family":"Eltahir","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, MaineHealth Institute for Research","place":["Scarborough, ME, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radfar","family":"Zohori","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, MaineHealth Institute for Research","place":["Scarborough, ME, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford J.","family":"Rosen","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, MaineHealth Institute for 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