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Nat Commun. 2017 Sep 12;8(1):417. doi: 10.1038/s41467-017-00462-2.

Misalignment with the external light environment drives metabolic and cardiac dysfunction.

Author information

1
Division of Diabetes, Endocrinology and Gastroenterology, School of Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, M13 9PL, UK.
2
Division of Diabetes, Endocrinology and Gastroenterology, School of Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, M13 9PL, UK. david.bechtold@manchester.ac.uk.

Abstract

Most organisms use internal biological clocks to match behavioural and physiological processes to specific phases of the day-night cycle. Central to this is the synchronisation of internal processes across multiple organ systems. Environmental desynchrony (e.g. shift work) profoundly impacts human health, increasing cardiovascular disease and diabetes risk, yet the underlying mechanisms remain unclear. Here, we characterise the impact of desynchrony between the internal clock and the external light-dark (LD) cycle on mammalian physiology. We reveal that even under stable LD environments, phase misalignment has a profound effect, with decreased metabolic efficiency and disrupted cardiac function including prolonged QT interval duration. Importantly, physiological dysfunction is not driven by disrupted core clock function, nor by an internal desynchrony between organs, but rather the altered phase relationship between the internal clockwork and the external environment. We suggest phase misalignment as a major driver of pathologies associated with shift work, chronotype and social jetlag.The misalignment between internal circadian rhythm and the day-night cycle can be caused by genetic, behavioural and environmental factors, and may have a profound impact on human physiology. Here West et al. show that desynchrony between the internal clock and the external environment alter metabolic parameters and cardiac function in mice.

PMID:
28900189
PMCID:
PMC5595905
DOI:
10.1038/s41467-017-00462-2
[Indexed for MEDLINE]
Free PMC Article

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