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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Dataset's files

Source:

			Action	DRS
	CIA_vs_N.txt	Txt
	FL1079_MSQ1593_20190218_TorynPoolman_Phospho_10.raw	Raw
	FL1079_MSQ1593_20190218_TorynPoolman_Phospho_11.raw	Raw
	FL1079_MSQ1593_20190218_TorynPoolman_Phospho_12.raw	Raw
	FL1079_MSQ1593_20190218_TorynPoolman_Phospho_13.raw	Raw

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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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