Reprogramming of Circadian Rhythms by Dietary Methionine Restriction

The circadian clock tightly interacts with cellular metabolism, and nutritional challenges can profoundly remodel its function. Dietary methionine restriction (MR) has been shown to improve metabolic health and extend lifespan. However, the effects of MR on the circadian clock and the underlying mechanisms have remained unclear. In this study, we uncover that methionine deprivation (MD) diet induces a remarkable reprogramming of hepatic circadian rhythms. Notably, the MD diet resets the oscillation of genes involved in the lipogenic pathway. Mechanistically, we demonstrate that the MD diet induces fluctuations of m6A mRNA methylation and reshapes epigenetic landscape. Surprisingly, the rhythms of gut microbiota metabolism are reshaped by the MD diet, and the gut microbiota partially mediates the effects of the MD diet on hepatic circadian rhythms. Together, these findings provide compelling evidence that dietary methionine restriction remodels circadian rhythms through the modulation of gene expression, RNA methylation, histone modification, and microbiota metabolism.