Analysis of Methyltransferase BUD23 in Energy Metabolism

Chronic inflammation is highly prevalent, and underpins the majority of human diseases. Inflammatory signals act on the circadian clock to effect a profound change in the circadian clock machinery, and surprisingly up to five times as many genes show a circadian oscillation in inflamed tissue than in healthy states.
The circadian clock controls up to 25% of metabolic pathways in diverse organ systems, often acting to regulate rate-limiting steps in metabolic cascades. The function of this clock is to permit anticipation of predictable changes in the environment for example sleep/wake cycles with attendant changes from fed to fasted state. Therefore the identification of a major role for inflammation in re-wiring the circadian clock, and altering the coupling of output pathways to clock phase is of major importance.
We propose that an initially adaptive response to inflammation requires regulation of the circadian clock, mediated by cross-talk between core clock components, regulators of energy metabolism, and inflammatory signals, to meet the bioenergetics demands of the inflammatory process. In chronic inflammation this change is maladaptive and imposes a bioenergetic cost, with consequences for inflammatory resolution, organismal energy metabolism, and also in the response to therapeutic
intervention.