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Period-independent novel circadian oscillators revealed by timed exercise and palatable meals.

ABSTRACT: The mammalian circadian system is a hierarchical network of oscillators organized to optimally coordinate behavior and physiology with daily environmental cycles. The suprachiasmatic nucleus (SCN) of the hypothalamus is at the top of this hierarchy, synchronizing to the environmental light-dark cycle, and coordinates the phases of peripheral clocks. The Period genes are critical components of the molecular timekeeping mechanism of these clocks. Circadian clocks are disabled in Period1/2/3 triple mutant mice, resulting in arrhythmic behavior in constant conditions. We uncovered rhythmic behavior in this mutant by simply exposing the mice to timed access to a palatable meal or running wheel. The emergent circadian behavior rhythms free-ran for many cycles under constant conditions without cyclic environmental cues. Together, these data demonstrate that the palatable meal-inducible circadian oscillator (PICO) and wheel-inducible circadian oscillator (WICO) are generated by non-canonical circadian clocks. Entrainment of these novel oscillators by palatable snacks and timed exercise could become novel therapeutics for human conditions caused by disruptions of the circadian clocks.

SUBMITTER: Flores DE

PROVIDER: S-EPMC4764932 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Period-independent novel circadian oscillators revealed by timed exercise and palatable meals.

Flôres Danilo E F L DE Bettilyon Crystal N CN Yamazaki Shin S

Scientific reports 20160224

The mammalian circadian system is a hierarchical network of oscillators organized to optimally coordinate behavior and physiology with daily environmental cycles. The suprachiasmatic nucleus (SCN) of the hypothalamus is at the top of this hierarchy, synchronizing to the environmental light-dark cycle, and coordinates the phases of peripheral clocks. The Period genes are critical components of the molecular timekeeping mechanism of these clocks. Circadian clocks are disabled in Period1/2/3 triple ...[more]

PMID: 26904978

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Project description:MotivationCircadian oscillations have been observed in animals, plants, fungi and cyanobacteria and play a fundamental role in coordinating the homeostasis and behavior of biological systems. Genetically encoded molecular clocks found in nearly every cell, based on negative transcription/translation feedback loops and involving only a dozen genes, play a central role in maintaining these oscillations. However, high-throughput gene expression experiments reveal that in a typical tissue, a much larger fraction ([Formula: see text]) of all transcripts oscillate with the day-night cycle and the oscillating species vary with tissue type suggesting that perhaps a much larger fraction of all transcripts, and perhaps also other molecular species, may bear the potential for circadian oscillations.ResultsTo better quantify the pervasiveness and plasticity of circadian oscillations, we conduct the first large-scale analysis aggregating the results of 18 circadian transcriptomic studies and 10 circadian metabolomic studies conducted in mice using different tissues and under different conditions. We find that over half of protein coding genes in the cell can produce transcripts that are circadian in at least one set of conditions and similarly for measured metabolites. Genetic or environmental perturbations can disrupt existing oscillations by changing their amplitudes and phases, suppressing them or giving rise to novel circadian oscillations. The oscillating species and their oscillations provide a characteristic signature of the physiological state of the corresponding cell/tissue. Molecular networks comprise many oscillator loops that have been sculpted by evolution over two trillion day-night cycles to have intrinsic circadian frequency. These oscillating loops are coupled by shared nodes in a large network of coupled circadian oscillators where the clock genes form a major hub. Cells can program and re-program their circadian repertoire through epigenetic and other mechanisms.Availability and implementationHigh-resolution and tissue/condition specific circadian data and networks available at http://circadiomics.igb.uci.edu.Contactpfbaldi@ics.uci.eduSupplementary informationSupplementary data are available at Bioinformatics online.

Dataset Information

Period-independent novel circadian oscillators revealed by timed exercise and palatable meals.

Publications

Period-independent novel circadian oscillators revealed by timed exercise and palatable meals.

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