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Hyperphosphatemia increases inflammation to exacerbate anemia and skeletal muscle wasting independently of FGF23-FGFR4 signaling

Elevations in plasma phosphate concentrations (hyperphosphatemia) occur in chronic kidney disease (CKD), in certain genetic disorders, and following the intake of a phosphate-rich diet. Whether hyperphosphatemia and/or associated changes in metabolic regulators, including elevations of fibroblast gr...

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Autores principales: Czaya, Brian, Heitman, Kylie, Campos, Isaac, Yanucil, Christopher, Kentrup, Dominik, Westbrook, David, Gutierrez, Orlando, Babitt, Jodie L, Jung, Grace, Salusky, Isidro B, Hanudel, Mark, Faul, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8963881/
https://www.ncbi.nlm.nih.gov/pubmed/35302487
http://dx.doi.org/10.7554/eLife.74782
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author Czaya, Brian
Heitman, Kylie
Campos, Isaac
Yanucil, Christopher
Kentrup, Dominik
Westbrook, David
Gutierrez, Orlando
Babitt, Jodie L
Jung, Grace
Salusky, Isidro B
Hanudel, Mark
Faul, Christian
author_facet Czaya, Brian
Heitman, Kylie
Campos, Isaac
Yanucil, Christopher
Kentrup, Dominik
Westbrook, David
Gutierrez, Orlando
Babitt, Jodie L
Jung, Grace
Salusky, Isidro B
Hanudel, Mark
Faul, Christian
author_sort Czaya, Brian
collection PubMed
description Elevations in plasma phosphate concentrations (hyperphosphatemia) occur in chronic kidney disease (CKD), in certain genetic disorders, and following the intake of a phosphate-rich diet. Whether hyperphosphatemia and/or associated changes in metabolic regulators, including elevations of fibroblast growth factor 23 (FGF23) directly contribute to specific complications of CKD is uncertain. Here, we report that similar to patients with CKD, mice with adenine-induced CKD develop inflammation, anemia, and skeletal muscle wasting. These complications are also observed in mice fed high phosphate diet even without CKD. Ablation of pathologic FGF23-FGFR4 signaling did not protect mice on an increased phosphate diet or mice with adenine-induced CKD from these sequelae. However, low phosphate diet ameliorated anemia and skeletal muscle wasting in a genetic mouse model of CKD. Our mechanistic in vitro studies indicate that phosphate elevations induce inflammatory signaling and increase hepcidin expression in hepatocytes, a potential causative link between hyperphosphatemia, anemia, and skeletal muscle dysfunction. Our study suggests that high phosphate intake, as caused by the consumption of processed food, may have harmful effects irrespective of pre-existing kidney injury, supporting not only the clinical utility of treating hyperphosphatemia in CKD patients but also arguing for limiting phosphate intake in healthy individuals.
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spelling pubmed-89638812022-03-30 Hyperphosphatemia increases inflammation to exacerbate anemia and skeletal muscle wasting independently of FGF23-FGFR4 signaling Czaya, Brian Heitman, Kylie Campos, Isaac Yanucil, Christopher Kentrup, Dominik Westbrook, David Gutierrez, Orlando Babitt, Jodie L Jung, Grace Salusky, Isidro B Hanudel, Mark Faul, Christian eLife Cell Biology Elevations in plasma phosphate concentrations (hyperphosphatemia) occur in chronic kidney disease (CKD), in certain genetic disorders, and following the intake of a phosphate-rich diet. Whether hyperphosphatemia and/or associated changes in metabolic regulators, including elevations of fibroblast growth factor 23 (FGF23) directly contribute to specific complications of CKD is uncertain. Here, we report that similar to patients with CKD, mice with adenine-induced CKD develop inflammation, anemia, and skeletal muscle wasting. These complications are also observed in mice fed high phosphate diet even without CKD. Ablation of pathologic FGF23-FGFR4 signaling did not protect mice on an increased phosphate diet or mice with adenine-induced CKD from these sequelae. However, low phosphate diet ameliorated anemia and skeletal muscle wasting in a genetic mouse model of CKD. Our mechanistic in vitro studies indicate that phosphate elevations induce inflammatory signaling and increase hepcidin expression in hepatocytes, a potential causative link between hyperphosphatemia, anemia, and skeletal muscle dysfunction. Our study suggests that high phosphate intake, as caused by the consumption of processed food, may have harmful effects irrespective of pre-existing kidney injury, supporting not only the clinical utility of treating hyperphosphatemia in CKD patients but also arguing for limiting phosphate intake in healthy individuals. eLife Sciences Publications, Ltd 2022-03-18 /pmc/articles/PMC8963881/ /pubmed/35302487 http://dx.doi.org/10.7554/eLife.74782 Text en © 2022, Czaya et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Czaya, Brian
Heitman, Kylie
Campos, Isaac
Yanucil, Christopher
Kentrup, Dominik
Westbrook, David
Gutierrez, Orlando
Babitt, Jodie L
Jung, Grace
Salusky, Isidro B
Hanudel, Mark
Faul, Christian
Hyperphosphatemia increases inflammation to exacerbate anemia and skeletal muscle wasting independently of FGF23-FGFR4 signaling
title Hyperphosphatemia increases inflammation to exacerbate anemia and skeletal muscle wasting independently of FGF23-FGFR4 signaling
title_full Hyperphosphatemia increases inflammation to exacerbate anemia and skeletal muscle wasting independently of FGF23-FGFR4 signaling
title_fullStr Hyperphosphatemia increases inflammation to exacerbate anemia and skeletal muscle wasting independently of FGF23-FGFR4 signaling
title_full_unstemmed Hyperphosphatemia increases inflammation to exacerbate anemia and skeletal muscle wasting independently of FGF23-FGFR4 signaling
title_short Hyperphosphatemia increases inflammation to exacerbate anemia and skeletal muscle wasting independently of FGF23-FGFR4 signaling
title_sort hyperphosphatemia increases inflammation to exacerbate anemia and skeletal muscle wasting independently of fgf23-fgfr4 signaling
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8963881/
https://www.ncbi.nlm.nih.gov/pubmed/35302487
http://dx.doi.org/10.7554/eLife.74782
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