Coordination of the transcriptome and metabolome by the circadian clock

The circadian clock governs a large array of physiological functions through the transcriptional control of a significant fraction of the genome. Disruption of the clock leads to metabolic disorders, including obesity and diabetes. As food is a potent Zeitgeber (ZT) for peripheral clocks, metabolite...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2012-04, Vol.109 (14), p.5541-5546
Main Authors: Eckel-Mahan, Kristin L., Patel, Vishal R., Mohney, Robert P., Vignola, Katie S., Baldi, Pierre, Sassone-Corsi, Paolo
Format: Article
Language:English
Subjects:
Amino acid metabolism
Amino acids
Animals
Biochemical pathways
Biological Sciences
Calorimetry
Carbohydrate metabolism
Cellular metabolism
Chromatin Immunoprecipitation
Circadian Clocks
Genotypes
Lipid metabolism
Liver
Male
Mass spectrometry
Metabolic disorders
Metabolism
Metabolites
Metabolome
Mice
Obesity
Protein metabolism
Transcriptome
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Summary:The circadian clock governs a large array of physiological functions through the transcriptional control of a significant fraction of the genome. Disruption of the clock leads to metabolic disorders, including obesity and diabetes. As food is a potent Zeitgeber (ZT) for peripheral clocks, metabolites are implicated as cellular transducers of circadian time for tissues such as the liver. From a comprehensive dataset of over 500 metabolites identified by mass spectrometry, we reveal the coordinate clock-controlled oscillation of many metabolites, including those within the amino acid and carbohydrate metabolic pathways as well as the lipid, nucleotide, and xenobiotic metabolic pathways. Using computational modeling, we present evidence of synergistic nodes between the circadian transcriptome and specific metabolic pathways. Validation of these nodes reveals that diverse metabolic pathways, including the uracil salvage pathway, oscillate in a circadian fashion and in a CLOCK-dependent manner. This integrated map illustrates the coherence within the circadian metabolome, transcriptome, and proteome and how these are connected through specific nodes that operate in concert to achieve metabolic homeostasis.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1118726109