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Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism

ABSTRACT: Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism

PROVIDER: PRJNA734946 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14715800_1.fastq.gz	Fastqsanger.gz
	SRR14715800_2.fastq.gz	Fastqsanger.gz
	SRR14715900_1.fastq.gz	Fastqsanger.gz
	SRR14715900_2.fastq.gz	Fastqsanger.gz
	SRR14716000_1.fastq.gz	Fastqsanger.gz

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Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism

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Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism

Project description: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.

2022-05-08 | PXD032723 | Pride

Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism.

Project 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.

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