title: Reprogramming of the circadian clock by nutritional challenge.
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.
authors.affiliation: Center for Epigenetics and Metabolism, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Eckel-Mahan
authors.affiliation: Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Vishal R
authors.initials: VR
authors.lastname: Patel
authors.affiliation: Center for Epigenetics and Metabolism, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: de Mateo
authors.affiliation: Center for Epigenetics and Metabolism, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Orozco-Solis
authors.affiliation: Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Ceglia
authors.affiliation: Center for Epigenetics and Metabolism, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Sahar
authors.affiliation: Center for Epigenetics and Metabolism, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Sherry A
authors.initials: SA
authors.lastname: Dilag-Penilla
authors.affiliation: Venetian Institute of Molecular Medicine, Padova 35129, Italy.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Dyar
authors.affiliation: Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Pierre
authors.initials: P
authors.lastname: Baldi
authors.affiliation: Center for Epigenetics and Metabolism, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: psc@uci.edu.
authors.forename: Paolo
authors.initials: P
authors.lastname: Sassone-Corsi
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism; D000818:Animals; D056926:CLOCK Proteins / Q000378:metabolism; D057906:Circadian Clocks; D002940:Circadian Rhythm; D059305:Diet, High-Fat; D005786:Gene Expression Regulation; D008297:Male; D053858:Metabolic Networks and Pathways; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D059467:Transcriptome
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D047495:PPAR gamma; D056926:CLOCK Proteins; C538944:Clock protein, mouse