Downton, P;
Sanna, F;
Maidstone, R;
Poolman, TM;
Hayter, EA;
Dickson, SH;
Ciccone, NA;
... Ray, DW; + view all
(2022)
Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism.
Proceedings of the National Academy of Sciences of the United States of America
, 119
(18)
, Article e2112781119. 10.1073/pnas.2112781119.
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Abstract
SignificanceRheumatoid arthritis (RA) is a debilitating chronic inflammatory disease in which symptoms exhibit a strong time-of-day rhythmicity. RA is commonly associated with metabolic disturbance and increased incidence of diabetes and cardiovascular disease, yet the mechanisms underlying this metabolic dysregulation remain unclear. Here, we demonstrate that rhythmic inflammation drives reorganization of metabolic programs in distal liver and muscle tissues. Chronic inflammation leads to mitochondrial dysfunction and dysregulation of fatty acid metabolism, including accumulation of inflammation-associated ceramide species in a time-of-day-dependent manner. These findings reveal multiple points for therapeutic intervention centered on the circadian clock, metabolic dysregulation, and inflammatory signaling.
| Type: | Article |
|---|---|
| Title: | Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1073/pnas.2112781119 |
| Publisher version: | https://doi.org/10.1073/pnas.2112781119 |
| Language: | English |
| Additional information: | Copyright © 2022 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY). |
| Keywords: | ceramide, circadian clock, inflammation, mitochondria, rheumatoid arthritis, Arthritis, Circadian Clocks, Circadian Rhythm, Energy Metabolism, Humans, Inflammation |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10148890 |
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