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Cell. 2013 Dec 19;155(7):1464-78. doi: 10.1016/j.cell.2013.11.034.

Reprogramming of the circadian clock by nutritional challenge.

Author information

1
Center for Epigenetics and Metabolism, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
2
Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, Irvine, CA 92697, USA.
3
Venetian Institute of Molecular Medicine, Padova 35129, Italy.
4
Center for Epigenetics and Metabolism, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: psc@uci.edu.

Abstract

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.

Comment in

PMID:
24360271
PMCID:
PMC4573395
DOI:
10.1016/j.cell.2013.11.034
[Indexed for MEDLINE]
Free PMC Article

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