Methionine Deprivation-induced Reprogramming of Hepatic Rhythms Is Partially Mediated by Glucocorticoid Receptor [RNAseq-TRF]

Dietary methionine restriction has been shown to improve metabolic health and extend lifespan. However, whether and how dietary methionine restriction impacts the circadian clock is unclear.

Here, we demonstrate that methionine deprivation (MD) induces dramatic alterations in two signaling systems that input to the circadian clock: de novo oscillation of circulating FGF21 coupled with increased amplitude of glucocorticoid oscillations. These alterations in signaling result in a remarkable reprogramming of the hepatic circadian transcriptome and epigenetic landscape. The epigenetic and transcriptomic alterations result from dramatic remodeling of the rhythmic binding of the glucocorticoid receptor (GR) to chromatin as they are abolished by liver-specific deletion of GR.