Reprogramming of the circadian clock by nutritional challenge
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 c...
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| Veröffentlicht in: | Cell Jg. 155; H. 7; S. 1464 |
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| Hauptverfasser: | , , , , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
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United States
19.12.2013
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| ISSN: | 1097-4172, 1097-4172 |
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| 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. |
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| AbstractList | 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.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. 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. |
| Author | Sassone-Corsi, Paolo Sahar, Saurabh Patel, Vishal R Dyar, Kenneth A Eckel-Mahan, Kristin L Baldi, Pierre Orozco-Solis, Ricardo Ceglia, Nicholas J de Mateo, Sara Dilag-Penilla, Sherry A |
| Author_xml | – sequence: 1 givenname: Kristin L surname: Eckel-Mahan fullname: Eckel-Mahan, Kristin L organization: Center for Epigenetics and Metabolism, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA – sequence: 2 givenname: Vishal R surname: Patel fullname: Patel, Vishal R organization: Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, Irvine, CA 92697, USA – sequence: 3 givenname: Sara surname: de Mateo fullname: de Mateo, Sara organization: Center for Epigenetics and Metabolism, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA – sequence: 4 givenname: Ricardo surname: Orozco-Solis fullname: Orozco-Solis, Ricardo organization: Center for Epigenetics and Metabolism, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA – sequence: 5 givenname: Nicholas J surname: Ceglia fullname: Ceglia, Nicholas J organization: Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, Irvine, CA 92697, USA – sequence: 6 givenname: Saurabh surname: Sahar fullname: Sahar, Saurabh organization: Center for Epigenetics and Metabolism, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA – sequence: 7 givenname: Sherry A surname: Dilag-Penilla fullname: Dilag-Penilla, Sherry A organization: Center for Epigenetics and Metabolism, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA – sequence: 8 givenname: Kenneth A surname: Dyar fullname: Dyar, Kenneth A organization: Venetian Institute of Molecular Medicine, Padova 35129, Italy – sequence: 9 givenname: Pierre surname: Baldi fullname: Baldi, Pierre organization: Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, Irvine, CA 92697, USA – sequence: 10 givenname: Paolo surname: Sassone-Corsi fullname: Sassone-Corsi, Paolo email: psc@uci.edu organization: Center for Epigenetics and Metabolism, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: psc@uci.edu |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24360271$$D View this record in MEDLINE/PubMed |
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| Title | Reprogramming of the circadian clock by nutritional challenge |
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