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Fibroblast growth factor 23 (FGF23), a bone hormone, regulates renal phosphate and vitamin D metabolism. Under pathophysiological conditions production of FGF23 is stimulated. HFD feeding elevates serum FGF23 levels through inflammation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Objective<\/jats:title>\n            <jats:p>We aimed to investigate whether HFD feeding and obesity is associated with gastric FGF23 production.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Mice were fed a standard diet or HFD for 12 weeks (long-term) or 1 week (short-term), and the stomachs were then examined. Additionally, corpus specimens from patients with obesity, human umbilical vein endothelial cells (HUVECs), and normal human gastric epithelial cells (GES-1) were studied. FGF23 production was examined by qPCR and Western blotting, mucosal integrity assessed by fluorescence microscopy, and FGF23-expressing cells analyzed by immunohistochemistry.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In mice, HFD feeding up-regulated <jats:italic>Fgf23<\/jats:italic> expression and FGF23 protein abundance in the proximal glandular stomach. FGF23-positive cells were detected in damaged glandular and interglandular areas representing mucus-like cells, endothelial cells of interconnected blood vessels or stromal endothelial cells and myofibroblasts. FGF23 expression was associated with impaired tissue integrity, immune cell infiltration and lipid deposition, with less pronounced mucosal changes upon short-term HFD feeding. Gastric FGF23 was also detectable in patients with obesity, mainly in endothelial cells of dilated and interconnected vessels. In HUVECs, pro-angiogenic adipokine leptin ramped up <jats:italic>FGF23<\/jats:italic> transcript levels. In GES-1 cells, proinflammatory cytokine interleukin-1\u03b2 (IL-1\u03b2) tended to enhance <jats:italic>FGF23<\/jats:italic> expression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>HFD feeding stimulates gastric FGF23 production and, in particular, increases the number of FGF23-expressing endothelial and epithelial cells.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1038\/s41366-025-01808-3","type":"journal-article","created":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T02:00:28Z","timestamp":1749261628000},"page":"1733-1744","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["High fat diet induces gastric production of fibroblast growth factor 23 (FGF23)"],"prefix":"10.1038","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7728-9194","authenticated-orcid":false,"given":"Patricia","family":"Widmayer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Feger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonie","family":"Meier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2723-5953","authenticated-orcid":false,"given":"Andreas H.","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2074-4827","authenticated-orcid":false,"given":"Michael","family":"F\u00f6ller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,6,7]]},"reference":[{"key":"1808_CR1","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.bone.2016.11.013","volume":"100","author":"M Kuro-O","year":"2017","unstructured":"Kuro-O M, Moe OW. 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The other authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Ethical approval was obtained from the Ethics Committee of the State Medical Council of Baden-W\u00fcrttemberg, Germany (F-2022-013) and from the Ethics Committee of the Medical Faculty of the University of T\u00fcbingen (485\/2007\/BO1). Research was conducted with the principles of the Declaration of Helsinki for biomedical research. Informed consent was obtained from all individual participants included in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Patients signed informed consent regarding publishing their data and photographs.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}