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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.

Original publication

DOI

10.1073/pnas.2112781119

Type

Journal article

Journal

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

Publication Date

05/2022

Volume

119

Addresses

Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PT, United Kingdom.

Keywords

Humans, Arthritis, Inflammation, Energy Metabolism, Circadian Rhythm, Circadian Clocks