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Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism

Skene, Debra, Skornyakov, Elena, Chowdhury, Namrata, Gajula, Rajendra P, Middleton, Benita, Satterfield, Brieann C, Porter, Kenneth I, Van Dongen, Hans P A and Gaddameedhi, Shobhan (2018) Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism PNAS, 115 (30). pp. 7825-7830.

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Abstract

Misalignment between internal circadian rhythmicity and externally imposed behavioral schedules, such as occurs in shift workers, has been implicated in elevated risk of metabolic disorders. To determine underlying mechanisms, it is esse ntial to assess whether and how peripheral clocks are disturbed during shift work and to what extent this is linked to the central suprachiasmatic nuclei (SCN) pacemaker and/or misaligned behavioral time cues. Investigating rhythms in circulating metabolites as biomarkers of peripheral clock distur- bances may offer new insight s. We evaluated the impact of misaligned sleep/wake and feeding/fasting cycles on circulating metabolites using a targeted metabolomics approach. Sequential plasma samples obtained during a 24-h constant routine that followed a 3-d simulated night-s hift schedule, compared with a simulated day-shift schedule, we re analyzed for 132 circulating metabolites. Nearly half of these metabolites showed a 24-h rhyth- micity under constant routine following either or both simulated shift schedules. However, while tradition al markers of the circadian clock in the SCN — melatonin, cortisol, and PER3 expression — maintained a stable phase alignment after both schedules, only a few metabo- lites did the same. Many showed reversed rhythms, lost their rhythms, or showed rhythmicity only under constant routine fol- lowing the night-shift schedule. Here, 95% of the metabolites with a 24-h rhythmicity showed rhythms that were driven by behavior- al time cues externally imposed during the preceding simulated shift schedule rather than being driven by the central SCN circa- dian clock. Characterization of these metabolite rhythms will pro- vide insight into the underlying mechanisms linking shift work and metabolic disorders

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Skene, DebraD.Skene@surrey.ac.uk
Skornyakov, Elena
Chowdhury, Namratanamrata.chowdhury@surrey.ac.uk
Gajula, Rajendra P
Middleton, BenitaB.Middleton@surrey.ac.uk
Satterfield, Brieann C
Porter, Kenneth I
Van Dongen, Hans P A
Gaddameedhi, Shobhan
Date : 10 July 2018
Funders : BBSRC
DOI : 10.1073/pnas.1801183115
Copyright Disclaimer : Copyright © 2018 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Depositing User : Melanie Hughes
Date Deposited : 19 Jul 2018 08:41
Last Modified : 11 Dec 2018 11:24
URI: http://epubs.surrey.ac.uk/id/eprint/848748

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