Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism.
Downton P., Sanna F., Maidstone R., Poolman TM., Hayter EA., Dickson SH., Ciccone NA., Early JO., Adamson A., Spiller DG., Simpkins DA., Baxter M., Fischer R., Rattray M., Loudon ASI., Gibbs JE., Bechtold DA., Ray DW.
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.