Dataset Information

Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism

ABSTRACT: Chronic inflammation underpins many human diseases. The morbidity and mortality of chronic inflammation is 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, here we show thatchronic 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 reveal alteration in lipid metabolism and mitochondrial function associated with increased EGFR-JAK11 STAT3 signalling. Metabolomic analyses confirmed rhythmic metabolic rewiring with impaired β-oxidation and lipid handling, and revealed a pronounced shunt towards sphingolipid and ceramide accumulation. The arthritis-related production of ceramides was most pronounced during the day, the time of peak inflammation and increased reliance on fatty acid oxidation. Thus, our data demonstrate that localised joint inflammation drives a time-of-day dependent build-up of bioactive lipid species driven by rhythmic inflammation and altered EGFR-STAT signalling.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Tissue, Paw

DISEASE(S): Rheumatoid Arthritis

SUBMITTER: Roman Fischer

LAB HEAD: Roman Fischer

PROVIDER: PXD032723 | Pride | 2022-05-08

REPOSITORIES: Pride

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Publications

Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism.

Downton Polly P Sanna Fabio F Maidstone Robert R Poolman Toryn M TM Hayter Edward A EA Dickson Suzanna H SH Ciccone Nick A NA Early James O JO Adamson Antony A Spiller David G DG Simpkins Devin A DA Baxter Matthew M Fischer Roman R Rattray Magnus M Loudon Andrew S I ASI Gibbs Julie E JE Bechtold David A DA Ray David W DW

Proceedings of the National Academy of Sciences of the United States of America 20220428 18

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 a ...[more]

PMID: 35482925

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Project description:Baker2013 - Cytokine Mediated Inflammation in Rheumatoid Arthritis This model by Baker M. 2013, describes the interaction between pro and anti-inflammatory cytokine signalling in rheumatoid arthritis. Using two ordinary differential equations, the first model [BIOMD0000000550] analyses bifurcation and describes different pathological states by altering inflammatory regulation parameters. The second model [BIOMD0000000549] includes the effect that ageing has on pro-inflammatory signalling, allowing for time-dependant properties and disease progression to be observed. The author also describes potential dosing for reversal of the disease state. This model is described in the article: Mathematical modelling of cytokine-mediated inflammation in rheumatoid arthritis. Baker M, Denman-Johnson S, Brook BS, Gaywood I, Owen MR. Math Med Biol 2013 Dec; 30(4): 311-337 Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease preferentially affecting the joints and leading, if untreated, to progressive joint damage and disability. Cytokines, a group of small inducible proteins, which act as intercellular messengers, are key regulators of the inflammation that characterizes RA. They can be classified into pro-inflammatory and anti-inflammatory groups. Numerous cytokines have been implicated in the regulation of RA with complex up and down regulatory interactions. This paper considers a two-variable model for the interactions between pro-inflammatory and anti-inflammatory cytokines, and demonstrates that mathematical modelling may be used to investigate the involvement of cytokines in the disease process. The model displays a range of possible behaviours, such as bistability and oscillations, which are strongly reminiscent of the behaviour of RA e.g. genetic susceptibility and remitting-relapsing disease. We also show that the dose regimen as well as the dose level are important factors in RA treatments. This model is hosted on BioModels Database and identified by: BIOMD0000000550. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Baker2013 - Cytokine Mediated Inflammation in Rheumatoid Arthritis - Age Dependant This model by Baker M. 2013, describes the interaction between pro and anti-inflammatory cytokine signalling in rheumatoid arthritis. Using two ordinary differential equations, the first model [BIOMD0000000550] analyses bifurcation and describes different pathological states by altering inflammatory regulation parameters. The second model [BIOMD0000000549] includes the effect that ageing has on pro-inflammatory signalling, allowing for time-dependant properties and disease progression to be observed. The author also describes potential dosing for reversal of the disease state. This model is described in the article: Mathematical modelling of cytokine-mediated inflammation in rheumatoid arthritis. Baker M, Denman-Johnson S, Brook BS, Gaywood I, Owen MR. Math Med Biol 2013 Dec; 30(4): 311-337 Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease preferentially affecting the joints and leading, if untreated, to progressive joint damage and disability. Cytokines, a group of small inducible proteins, which act as intercellular messengers, are key regulators of the inflammation that characterizes RA. They can be classified into pro-inflammatory and anti-inflammatory groups. Numerous cytokines have been implicated in the regulation of RA with complex up and down regulatory interactions. This paper considers a two-variable model for the interactions between pro-inflammatory and anti-inflammatory cytokines, and demonstrates that mathematical modelling may be used to investigate the involvement of cytokines in the disease process. The model displays a range of possible behaviours, such as bistability and oscillations, which are strongly reminiscent of the behaviour of RA e.g. genetic susceptibility and remitting-relapsing disease. We also show that the dose regimen as well as the dose level are important factors in RA treatments. This model is hosted on BioModels Database and identified by: BIOMD0000000549. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism

Publications

Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism.

Similar Datasets

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