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Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism
Chronic inflammation underpins many human diseases. Morbidity and mortality associated with chronic inflammation are often mediated through metabolic dysfunction. Inflammatory and metabolic processes vary through circadian time, suggesting an important temporal crosstalk between these systems. Using...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170023/ https://www.ncbi.nlm.nih.gov/pubmed/35482925 http://dx.doi.org/10.1073/pnas.2112781119 |
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author | Downton, Polly Sanna, Fabio Maidstone, Robert Poolman, Toryn M. Hayter, Edward A. Dickson, Suzanna H. Ciccone, Nick A. Early, James O. Adamson, Antony Spiller, David G. Simpkins, Devin A. Baxter, Matthew Fischer, Roman Rattray, Magnus Loudon, Andrew S. I. Gibbs, Julie E. Bechtold, David A. Ray, David W. |
author_facet | Downton, Polly Sanna, Fabio Maidstone, Robert Poolman, Toryn M. Hayter, Edward A. Dickson, Suzanna H. Ciccone, Nick A. Early, James O. Adamson, Antony Spiller, David G. Simpkins, Devin A. Baxter, Matthew Fischer, Roman Rattray, Magnus Loudon, Andrew S. I. Gibbs, Julie E. Bechtold, David A. Ray, David W. |
author_sort | Downton, Polly |
collection | PubMed |
description | Chronic inflammation underpins many human diseases. Morbidity and mortality associated with chronic inflammation are often mediated through metabolic dysfunction. Inflammatory and metabolic processes vary through circadian time, suggesting an important temporal crosstalk between these systems. Using an established mouse model of rheumatoid arthritis, we show that chronic inflammatory arthritis results in rhythmic joint inflammation and drives major changes in muscle and liver energy metabolism and rhythmic gene expression. Transcriptional and phosphoproteomic analyses revealed alterations in lipid metabolism and mitochondrial function associated with increased EGFR-JAK-STAT3 signaling. Metabolomic analyses confirmed rhythmic metabolic rewiring with impaired β-oxidation and lipid handling and revealed a pronounced shunt toward sphingolipid and ceramide accumulation. The arthritis-related production of ceramides was most pronounced during the day, which is the time of peak inflammation and increased reliance on fatty acid oxidation. Thus, our data demonstrate that localized joint inflammation drives a time-of-day–dependent build-up of bioactive lipid species driven by rhythmic inflammation and altered EGFR-STAT signaling. |
format | Online Article Text |
id | pubmed-9170023 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-91700232022-06-07 Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism Downton, Polly Sanna, Fabio Maidstone, Robert Poolman, Toryn M. Hayter, Edward A. Dickson, Suzanna H. Ciccone, Nick A. Early, James O. Adamson, Antony Spiller, David G. Simpkins, Devin A. Baxter, Matthew Fischer, Roman Rattray, Magnus Loudon, Andrew S. I. Gibbs, Julie E. Bechtold, David A. Ray, David W. Proc Natl Acad Sci U S A Biological Sciences Chronic inflammation underpins many human diseases. Morbidity and mortality associated with chronic inflammation are often mediated through metabolic dysfunction. Inflammatory and metabolic processes vary through circadian time, suggesting an important temporal crosstalk between these systems. Using an established mouse model of rheumatoid arthritis, we show that chronic inflammatory arthritis results in rhythmic joint inflammation and drives major changes in muscle and liver energy metabolism and rhythmic gene expression. Transcriptional and phosphoproteomic analyses revealed alterations in lipid metabolism and mitochondrial function associated with increased EGFR-JAK-STAT3 signaling. Metabolomic analyses confirmed rhythmic metabolic rewiring with impaired β-oxidation and lipid handling and revealed a pronounced shunt toward sphingolipid and ceramide accumulation. The arthritis-related production of ceramides was most pronounced during the day, which is the time of peak inflammation and increased reliance on fatty acid oxidation. Thus, our data demonstrate that localized joint inflammation drives a time-of-day–dependent build-up of bioactive lipid species driven by rhythmic inflammation and altered EGFR-STAT signaling. National Academy of Sciences 2022-04-28 2022-05-03 /pmc/articles/PMC9170023/ /pubmed/35482925 http://dx.doi.org/10.1073/pnas.2112781119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Biological Sciences Downton, Polly Sanna, Fabio Maidstone, Robert Poolman, Toryn M. Hayter, Edward A. Dickson, Suzanna H. Ciccone, Nick A. Early, James O. Adamson, Antony Spiller, David G. Simpkins, Devin A. Baxter, Matthew Fischer, Roman Rattray, Magnus Loudon, Andrew S. I. Gibbs, Julie E. Bechtold, David A. Ray, David W. Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism |
title | Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism |
title_full | Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism |
title_fullStr | Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism |
title_full_unstemmed | Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism |
title_short | Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism |
title_sort | chronic inflammatory arthritis drives systemic changes in circadian energy metabolism |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170023/ https://www.ncbi.nlm.nih.gov/pubmed/35482925 http://dx.doi.org/10.1073/pnas.2112781119 |
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