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High fat diet induces gastric production of fibroblast growth factor 23 (FGF23)

P. Widmayer,Martina Feger,Leonie Meier,A.H. Wagner,Michael Föller

Published 2025 in International Journal of Obesity

ABSTRACT

A high fat diet (HFD) leads to lesions of the gastric epithelium and causes a proinflammatory environment. 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. We aimed to investigate whether HFD feeding and obesity is associated with gastric FGF23 production. 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. In mice, HFD feeding up-regulated Fgf23 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 FGF23 transcript levels. In GES-1 cells, proinflammatory cytokine interleukin-1β (IL-1β) tended to enhance FGF23 expression. HFD feeding stimulates gastric FGF23 production and, in particular, increases the number of FGF23-expressing endothelial and epithelial cells.

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