Reprogramming of the Circadian Clock by Nutritional Challenge
By Kristin L. Eckel-Mahan, Vishal R. Patel, S. de Mateo, R. Orozco-Solís, Nicholas Ceglia, Saurabh Sahar, Sherry Dilag, K. Dyar, Pierre Baldi, Paolo Sassone-Corsi. Cell, 2013
692 citations recorded by the source corpus.
Summary Circadian rhythms and cellular metabolism are intimately linked. Here we reveal that a high-fat diet (HFD) generates a profound reorganization of specific metabolic pathways, leading to widespread remodeling of the liver clock. Strikingly, in addition to disrupting the normal circadian cycle, HFD causes an unexpectedly large-scale genesis of de novo oscillating transcripts, resulting in reorganization of the coordinated oscillations between coherent transcripts and metabolites. The mechanisms underlying this reprogramming involve both the impairment of CLOCK:BMAL1 chromatin recruitment, and a pronounced cyclic activation of surrogate pathways through the transcriptional regulator PPARγ. Finally, we demonstrate that it is specifically the nutritional challenge, and not the development of obesity, that causes the reprogramming of the clock and that the effects of the diet on the clock are reversible.
Subfields: Aging, Endocrine and Autonomic Systems, Physiology
View Paper: https://www.semanticscholar.org/paper/e30136a6fcabf755cfce770b41029023d4752c22
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Citations in the corpus
- Effects of diurnal variation of gut microbes and high fat feeding on host circadian clock function and metabolism (2015, neutral): “Contrary to the MBH responses, HF suppressed bmal1 expression in the liver (Figure 1E, ZT2, 18, and 22), blunting the hepatic CC pattern, as previously shown (Kohsaka et al., 2007; Eckel-Mahan et al., 2013).”
- Promoting Health and Longevity through Diet: from Model Organisms to Humans (2015, positive): “Interestingly, a diet high in fat induces a rapid and reversible impairment of BMAL1 recruitment to target chromatin sites and modifies circadian transcriptome and metabolome profiles (Eckel-Mahan et al., 2013).”