A high-fat diet stimulates fibroblast growth factor 23 formation in mice through TNFα upregulation

Glosse, Philipp; Fajol, Abul; Hirche, Frank; Feger, Martina; Voelkl, Jakob; Läng, Florian; Stangl, Gabriele I.; Föller, Michael

doi:10.1038/s41387-018-0037-x

Cited by 36 publications

(29 citation statements)

References 29 publications

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“…These results suggest that inflammation could be a trigger of FGF23 production. Indeed, proinflammatory cytokines including tumour necrosis factor α (TNFα), interleukin (IL)1β/6, and other inflammation‐associated molecules including bacterial lipopolysaccharides (LPS), other bacterial components or their toxins and advanced glycation end products (AGEs) upregulate Fgf23 gene expression directly and dose‐dependently (Fig. ).…”

Section: Homeostatic Regulation Of Fgf23mentioning

confidence: 99%

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Regulation of fibroblast growth factor 23 (FGF23) in health and disease

et al. 2019

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Fibroblast growth factor 23 (FGF23) is mainly produced in the bone and, upon secretion, forms a complex with a FGF receptor and coreceptor αKlotho. FGF23 can exert several endocrine functions, such as inhibiting renal phosphate reabsorption and 1,25‐dihydroxyvitamin D3 production. Moreover, it has paracrine activities on several cell types, including neutrophils and hepatocytes. Klotho and Fgf23 deficiencies result in pathologies otherwise encountered in age‐associated diseases, mainly as a result of hyperphosphataemia‐dependent calcification. FGF23 levels are also perturbed in the plasma of patients with several disorders, including kidney or cardiovascular diseases. Here, we review mechanisms controlling FGF23 production and discuss how FGF23 regulation is perturbed in disease.

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Section: Homeostatic Regulation Of Fgf23mentioning

confidence: 99%

“…A diet rich in high fats elevates the serum FGF23 level in rodents , at least in part through enhanced inflammation .…”

Section: Homeostatic Regulation Of Fgf23mentioning

confidence: 99%

Regulation of fibroblast growth factor 23 (FGF23) in health and disease

et al. 2019

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“…In humans, serum levels of FGF23 increase with higher body mass index and fat mass, and FGF23 levels were higher in individuals with metabolic syndrome [50]. In mouse models, HFD feeding significantly increased FGF23 that was dependent on upregulated tumor necrosis factor-α signaling [51]. In RCD-fed mice, we observed a trend for an increase in the c-terminal FGF23 and no changes in intact FGF23 levels, but in HFD-fed mice, serum levels of both c-terminal and intact FGF23 were significantly elevated.…”

Section: Discussionmentioning

confidence: 97%

Erythropoietin-Induced Changes in Bone and Bone Marrow in Mouse Models of Diet-Induced Obesity

Suresh

Alvarez

Dey

et al. 2020

IJMS

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Obesity remodels bone and increases bone marrow adipocytes (BMAT), which negatively regulate hematopoiesis and bone. Reduced BMAT could restore altered hematopoiesis and bone features. We analyzed the potential of erythropoietin (EPO), the cytokine required for erythropoiesis, to inhibit BMAT in C57BL6/J mice fed four weeks of a high-fat diet (HFD). Acute EPO administration markedly decreased BMAT in regular chow diet (RCD) and HFD-fed mice, without affecting whole body fat mass. Micro-CT analysis showed EPO reduced trabecular bone in RCD- and HFD-fed mice, but EPO-treated HFD-fed mice maintained cortical bone mineral density and cortical bone volume, which was reduced on RCD. Despite achieving similar increased hematocrits with BMAT loss in RCD- and HFD-fed mice treated with EPO, decreased bone marrow cellularity was only observed in RCD-fed mice concomitant with an increasing percentage of bone marrow erythroid cells. In contrast, in HFD-fed mice, EPO increased endothelial cells and stromal progenitors with a trend toward the normalization of marrow homeostasis. EPO administration increased c-terminal FGF23 and intact serum FGF23 only in HFD-fed mice. These data demonstrate the distinct EPO responses of bone and marrow in normal and obese states, accompanying EPO-induced loss of BMAT.

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“…The increase of FGF23 plasma levels following high-fat diet is at least partially due to upregulation of TNFα [12].…”

Section: Stimulators Of Fgf23 Releasementioning

confidence: 99%

Phosphate Homeostasis, Inflammation and the Regulation of FGF-23

Läng

Leibrock

Pandyra

et al. 2018

Kidney Blood Press Res

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Fibroblast growth factor 23 (FGF23) is released primarily from osteoblasts/osteocytes in bone. In cooperation with the transmembrane protein Klotho, FGF23 is a powerful inhibitor of 1α 25OH Vitamin D Hydroxylase (Cyp27b1) and thus of the formation of 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃). As 1,25(OH)₂D₃ up-regulates intestinal calcium and phosphate absorption, the downregulation of 1,25(OH)₂D₃ synthesis counteracts phosphate excess and tissue calcification. FGF23 also directly inhibits renal phosphate reabsorption. Other actions of FGF23 include triggering of cardiac hypertrophy. FGF23 formation and/or release are stimulated by 1,25(OH)₂D₃, phosphate excess, Ca²⁺, PTH, leptin, catecholamines, mineralocorticoids, volume depletion, lithium, high fat diet, iron deficiency, TNFα and TGFß2. The stimulating effect of 1,25(OH)₂D₃ on FGF23 expression is dependent on RAC1/PAK1 induced actin-polymerisation. Intracellular signaling involved in the stimulation of FGF23 release also includes increases in the cytosolic Ca²⁺ concentration ([Ca²⁺]i) following intracellular Ca²⁺ release and store-operated Ca²⁺ entry (SOCE). SOCE is accomplished by the Ca²⁺ release-activated calcium channel protein 1 (Orai1) and its stimulator stromal interaction molecule 1 (STIM1). Expression of Orai1, SOCE and FGF23-formation are up-regulated by the proinflammatory transcription factor NFκB. The present brief review describes the cellular mechanisms involved in FGF23 regulation and its sensitivity to both phosphate metabolism and inflammation. The case is made that up-regulation of FGF23 by inflammatory mediators and signaling may amplify inflammation by inhibiting formation of the anti-inflammatory 1,25(OH)₂D₃.

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A high-fat diet stimulates fibroblast growth factor 23 formation in mice through TNFα upregulation

Cited by 36 publications

References 29 publications

Regulation of fibroblast growth factor 23 (FGF23) in health and disease

Regulation of fibroblast growth factor 23 (FGF23) in health and disease

Erythropoietin-Induced Changes in Bone and Bone Marrow in Mouse Models of Diet-Induced Obesity

Phosphate Homeostasis, Inflammation and the Regulation of FGF-23

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