Nuclear receptor REVERBα is a state-dependent regulator of liver energy metabolism
Louise Hunter, Charlotte E Pelekanou, Antony Adamson, Polly Downton, Nichola J. Barron, Thomas Cornfield, Toryn Poolman, Neil Humphreys, Peter S. Cunningham, Leanne Hodson, Andrew Loudon, Mudassar Iqbal, David A. Bechtold, David Ray
Abstract
Significance The circadian clock protein REVERBα is proposed to be a key regulator of liver metabolism. We now show that REVERBα action is critically dependent on metabolic state. Using transgenic mouse models, we show that the true role of REVERBα is to buffer against aberrant responses to metabolic perturbation, rather than confer rhythmic regulation to programs of lipid synthesis and storage, as has been thought previously. Thus, in the case of liver metabolism, the clock does not so much drive rhythmic processes, as provide protection against mistimed feeding cues. Understanding how the clock is coupled to metabolism is critical for understanding metabolic disease and the impacts of circadian disruptors such as shift work and 24-h lifestyles.