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
Hauptverfasser: Eckel-Mahan, Kristin L, Patel, Vishal R, de Mateo, Sara, Orozco-Solis, Ricardo, Ceglia, Nicholas J, Sahar, Saurabh, Dilag-Penilla, Sherry A, Dyar, Kenneth A, Baldi, Pierre, Sassone-Corsi, Paolo
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 19.12.2013
Schlagworte:
Animals
ARNTL Transcription Factors - metabolism
Circadian Clocks
Circadian Rhythm
CLOCK Proteins - metabolism
Diet, High-Fat
Gene Expression Regulation
Male
Metabolic Networks and Pathways
Mice
Mice, Inbred C57BL
Obesity - metabolism
PPAR gamma - metabolism
Transcriptome
ISSN:1097-4172, 1097-4172
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2013.11.034