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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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Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism

2022-04-05 | GSE176095 | GEO

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

Molecular profiles of Systemic Juvenile Idiopathic Arthritis patients

Project description:Biomarker identification for diagnosis of systemic juvenile idiopathic arthritis (SJIA), an auto-inflammatory disease that presents with prolonged fevers. Disease vs. healthy control

2015-09-03 | E-GEOD-57183 | biostudies-arrayexpress

Molecular profiles of Systemic Juvenile Idiopathic Arthritis patients

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2023-03-01 | GSE211612 | GEO

Multiomics reveals multilevel control of renal and systemic metabolism by the renal tubular circadian clock

Project description:Circadian rhythmicity in renal function suggests rhythmic adaptations in renal metabolism. To decipher the role of the circadian clock in renal metabolism, we studied diurnal changes in renal metabolic pathways using integrated transcriptomic, proteomic, and metabolomic analysis performed on control mice and mice with inducible deletion of the circadian clock regulator Bmal1 in the renal tubule (cKOt). With this unique resource, we demonstrated that ~30% RNAs, ~20% proteins and ~20% metabolites are rhythmic in kidneys of control mice. Several key metabolic pathways including NAD+ biosynthesis, fatty acid transport, carnitine shuttle, and b-oxidation displayed impairments in kidneys of cKOt, resulting in a perturbed mitochondrial activity. Carnitine reabsorption from the primary urine was one of the most impacted processes with a ~50% reduction in plasma carnitine levels and a parallel systemic decrease in tissues carnitine content. This suggests that the circadian clock in the renal tubule controls both kidney and systemic physiology.

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Transcriptionally regulated energy metabolism drives early erythropoiesis

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Project description:Comaprison of PBMCs from patients with systemic juvenile idiopathic arthritis during active and inactive disease

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