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

BACKGROUND/OBJECTIVES: Bone-derived fibroblast growth factor 23 (FGF23) is a hormone that suppresses renal phosphate reabsorption and calcitriol (i.e., 1,25(OH)(2)D(3)) formation together with its co-receptor Klotho. FGF23- or Klotho-deficient mice suffer from rapid aging with multiple age-associate...

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Autores principales: Glosse, Philipp, Fajol, Abul, Hirche, Frank, Feger, Martina, Voelkl, Jakob, Lang, Florian, Stangl, Gabriele I., Föller, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972144/
https://www.ncbi.nlm.nih.gov/pubmed/29807981
http://dx.doi.org/10.1038/s41387-018-0037-x
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author Glosse, Philipp
Fajol, Abul
Hirche, Frank
Feger, Martina
Voelkl, Jakob
Lang, Florian
Stangl, Gabriele I.
Föller, Michael
author_facet Glosse, Philipp
Fajol, Abul
Hirche, Frank
Feger, Martina
Voelkl, Jakob
Lang, Florian
Stangl, Gabriele I.
Föller, Michael
author_sort Glosse, Philipp
collection PubMed
description BACKGROUND/OBJECTIVES: Bone-derived fibroblast growth factor 23 (FGF23) is a hormone that suppresses renal phosphate reabsorption and calcitriol (i.e., 1,25(OH)(2)D(3)) formation together with its co-receptor Klotho. FGF23- or Klotho-deficient mice suffer from rapid aging with multiple age-associated diseases, at least in part due to massive calcification. FGF23 is considered as a disease biomarker since elevated plasma levels are observed early in patients with acute and chronic disorders including renal, cardiovascular, inflammatory, and metabolic diseases. An energy-dense diet, which induces sequelae of the metabolic syndrome in humans and mice at least in part by enhancing pro-inflammatory TNFα formation, has recently been demonstrated to stimulate FGF23 production. METHODS: We investigated the relevance of TNFα for high-fat diet (HFD)-induced FGF23 formation in wild-type (tnf(+/+)) and TNFα-deficient (tnf(−/−)) mice. RESULTS: Within 3 weeks, HFD feeding resulted in a strong increase in the serum FGF23 level in tnf(+/+) mice. Moreover, it caused low-grade inflammation as evident from a surge in hepatic Tnfα transcript levels. TNFα stimulated Fgf23 transcription in UMR106 osteoblast-like cells. Serum FGF23 was significantly lower in tnf(−/−) mice compared to tnf(+/+) mice following HFD. Serum phosphate and calcitriol were not significantly affected by genotype or diet. CONCLUSIONS: We show that HFD feeding is a powerful stimulator of murine FGF23 production through TNFα formation.
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spelling pubmed-59721442018-05-29 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 Lang, Florian Stangl, Gabriele I. Föller, Michael Nutr Diabetes Article BACKGROUND/OBJECTIVES: Bone-derived fibroblast growth factor 23 (FGF23) is a hormone that suppresses renal phosphate reabsorption and calcitriol (i.e., 1,25(OH)(2)D(3)) formation together with its co-receptor Klotho. FGF23- or Klotho-deficient mice suffer from rapid aging with multiple age-associated diseases, at least in part due to massive calcification. FGF23 is considered as a disease biomarker since elevated plasma levels are observed early in patients with acute and chronic disorders including renal, cardiovascular, inflammatory, and metabolic diseases. An energy-dense diet, which induces sequelae of the metabolic syndrome in humans and mice at least in part by enhancing pro-inflammatory TNFα formation, has recently been demonstrated to stimulate FGF23 production. METHODS: We investigated the relevance of TNFα for high-fat diet (HFD)-induced FGF23 formation in wild-type (tnf(+/+)) and TNFα-deficient (tnf(−/−)) mice. RESULTS: Within 3 weeks, HFD feeding resulted in a strong increase in the serum FGF23 level in tnf(+/+) mice. Moreover, it caused low-grade inflammation as evident from a surge in hepatic Tnfα transcript levels. TNFα stimulated Fgf23 transcription in UMR106 osteoblast-like cells. Serum FGF23 was significantly lower in tnf(−/−) mice compared to tnf(+/+) mice following HFD. Serum phosphate and calcitriol were not significantly affected by genotype or diet. CONCLUSIONS: We show that HFD feeding is a powerful stimulator of murine FGF23 production through TNFα formation. Nature Publishing Group UK 2018-05-29 /pmc/articles/PMC5972144/ /pubmed/29807981 http://dx.doi.org/10.1038/s41387-018-0037-x Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Glosse, Philipp
Fajol, Abul
Hirche, Frank
Feger, Martina
Voelkl, Jakob
Lang, Florian
Stangl, Gabriele I.
Föller, Michael
A high-fat diet stimulates fibroblast growth factor 23 formation in mice through TNFα upregulation
title A high-fat diet stimulates fibroblast growth factor 23 formation in mice through TNFα upregulation
title_full A high-fat diet stimulates fibroblast growth factor 23 formation in mice through TNFα upregulation
title_fullStr A high-fat diet stimulates fibroblast growth factor 23 formation in mice through TNFα upregulation
title_full_unstemmed A high-fat diet stimulates fibroblast growth factor 23 formation in mice through TNFα upregulation
title_short A high-fat diet stimulates fibroblast growth factor 23 formation in mice through TNFα upregulation
title_sort high-fat diet stimulates fibroblast growth factor 23 formation in mice through tnfα upregulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972144/
https://www.ncbi.nlm.nih.gov/pubmed/29807981
http://dx.doi.org/10.1038/s41387-018-0037-x
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