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Circadian blueprint of metabolic pathways in the brain

Abstract

The circadian clock is an endogenous, time-tracking system that directs multiple metabolic and physiological functions required for homeostasis. The master or central clock located within the suprachiasmatic nucleus in the hypothalamus governs peripheral clocks present in all systemic tissues, contributing to their alignment and ultimately to temporal coordination of physiology. Accumulating evidence reveals the presence of additional clocks in the brain and suggests the possibility that circadian circuits may feed back to these from the periphery. Here, we highlight recent advances in the communications between clocks and discuss how they relate to circadian physiology and metabolism.

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Fig. 1: Molecular organization of the mammalian circadian clock.
Fig. 2: Metabolic coupling of neurons and astrocytes.
Fig. 3: Network of hypothalamic oscillators.
Fig. 4: Interplay between peripheral and central clocks.

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Acknowledgements

The authors thank all members of the Sassone–Corsi laboratory for helpful discussions. Funding for C.M.G. was provided by the National Cancer Institute of the US National Institutes of Health (NIH T32 2T32CA009054-36A1) and by the European Research Council (ERC MSCA-IF-2016 MetEpiClock 749869). Financial support for P.S.-C. was provided by the National Institute of Health, INSERM, a KAUST–UCI partnership and a Novo Nordisk Challenge Grant.

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P.S.-C. and C.M.G. researched data for article, made substantial contributions to discussion of content and wrote, reviewed and edited the manuscript before submission.

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Glossary

Promoter element

The proximal DNA regulatory element immediately upstream of the transcription start site (TSS).

Chromatin transitions

Promoter elements governed by specific epigenetic modifications that can shift from an ‘active’ accessible state to a ‘repressed’ state and vice versa.

Oscillators

Timing systems composed of transcriptional and translational feedback loops with an endogenous periodicity of approximately 24 hours.

Hyperphagic

Characterized by an abnormal increase of food consumption.

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Greco, C.M., Sassone–Corsi, P. Circadian blueprint of metabolic pathways in the brain. Nat Rev Neurosci 20, 71–82 (2019). https://doi.org/10.1038/s41583-018-0096-y

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