Endocrine Abstracts (2017) 50 MTE4 | DOI: 10.1530/endoabs.50.MTE4

Controlling for diurnal variation

David Ray

University of Manchester, Manchester, UK.

We all live in an oscillating environment driven by the Earth’s rotation. This imposes predictable patterns of light and dark, to which almost all of life responds. There is a survival advantage in anticipating such environmental change, which has led to evolution of the autonomous circadian clock.

The circadian clock controls up to 40% of biochemical pathways, often acting to control a rate-limiting enzymatic step. Therefore, design and interpretation of biological experiments and clinical practice require acknowledgement of the power of the underlying circadian clock.

At the simplest level recording the time at which experiments are performed in relation to external cues, such as lights on (zeitgeber time; ZT), or clock time is important, to allow readers to assess and compare data. Amid concern about experimental reproducibility in biomedical research such recording should be mandated.

The core circadian clock in vertebrates is entrained by neural input from the retina to the light-dark cycle. However, the core clock is robustly buffered, and can only shift incrementally in response to changes in light-dark timing, such delayed transitions results in jet-lag. Typically two weeks acclimatization to a new light-dark schedule ensures full entrainment.

In addition, food availability is a powerful timing signal, and restricted feeding paradigms can be used to shift the liver metabolic clock to run out of phase with the central clock, e.g. by feeding nocturnal mice only during the day. Human studies can also be impacted by circadian factors, with major time of day variation in glucose tolerance, inflammation, and fat metabolism to name a few. Developments in biomarkers, and drug trials both require consideration of circadian machinery to reduce noise, and to maximize therapeutic index respectively.

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