The word circadian is derived from the Latin circa, meaning around, and dies, meaning day: around the day. All organisms on the planet have an organisation of physiological processes based on the two distinct environmental contrasts that occur as a result of Earth’s 24-hour daily rotation: night and day, dark and light. These contrasts are accompanied with other environmental changes relevant to any species, including food availability, temperature, and susceptibility to predation.

The ability to anticipate changes in the environment confers a distinct evolutionary advantage on any species. Physiological processes and behaviours follow circadian rhythms corresponding to the 24-hour cycle of light and darkness, and are entrained by various “zeitgebers” [the term in the research field, German for “time giver”] of time of day. In humans, the light period is also the waking phase, active phase, and phase of food foraging and consumption. The dark period is the sleeping phase, inactive phase, and fasting phase.

The master controller of the circadian “clock” is located in a region of the hypothalamus known as the suprachiasmatic nucleus [SCN]. The primary environmental factor driving circadian entrainment in the SCN is light: a specialised set of retinal cells communicate information about light to the SCN indicating whether it is day or night. Picture a blue sky on a clear day – that colour is not random to human physiology, it is a specific wavelength of shortwave blue light of 460-480 nanometers which provides the strongest signal to the SCN that it is the day/waking/active phase, [1]. Based on what input the SCN receives, it will synchronise the appropriate physiological requirements of that period to the light cues –,to wake, to eat, to digest, energy availability and storage [2].

However, peripheral tissues – including the liver, kidneys, pancreas, muscle, and adipose tissues – are also entrained by timing of food intake. The circadian system relies on synchrony between the central and peripheral clocks for optimal physiological function [3]. Thus, the inputs are vital to the integrity of our circadian system, and sending different or unusual inputs – inconsistent light signals, irregular meal patterns, curtailed sleep – can alter the outputs, including hormonal secretions, substrate oxidation and storage, hunger and appetite [3].

It is well established in the literature that circadian desynchronization, for example from shift work, is a primary risk factor for cardiometabolic disease [4]. This is because when food intake is desynchronized from the normally dichotomous circadian patterns of day/light/feed/active and night/dark/fast/inactive, control of metabolic processes become decoupled from the SCN, which is primarily entrained to light signals as opposed to food intake [3]. Traditionally, the focus of research into the importance of the circadian system for metabolic health focused on extreme situations like jet-lag and shift work. However, the effects of less extreme perturbations on metabolic health are coming to light.

 

Associations Between Circadian Disruption and Metabolic Health

As light is the primary time cue for the central clock, exposure to light has implications for metabolic health, potentially both positive and negative depending on timing of exposure. People in industrialised societies spend up to 88% of time in enclosed buildings, resulting in 4-fold less natural light exposure during the day [5][6]. To give you some perspective on this, light is measured in ‘lux’, and natural daytime light can be anywhere between 2,000 to 10,000lux while average indoor lighting can be less than 500lux, which lacks the minimum level of intensity for circadian entrainment [7]. Recent associative studies have found that greater morning light exposure correlates to lower body fat levels and better appetite regulation [1][20].

Conversely, at nighttime people in industrialized societies are exposed to artificial light, in particular from electronic devices which emit shortwave blue light, the very same light intensity emitted during the day. Melatonin, the primary hormone produced at night in response to darkness, is maximally suppressed by shortwave blue light [1]. This may be problematic as melatonin receptors have been identified in the pancreas and modulate insulin secretion [8]. In the Nurses’ Health Study, women with the lowest melatonin levels at baseline were more likely to have developed T2DM when followed up with 12 years later [9]. The effects of this alteration in our natural light environments and normally dichotomous periods of wake/sleep coinciding with feed/fast are both indirect and direct.

Indirect effects include ‘social jetlag’, and the effect of extended evening illumination on meal timing. ‘Social jetlag’ is the discrepancy between actual sleep time during the week, with enforced early waking or late evenings, and how much sleep an individual would actually need if they were to sleep freely. The issue is that many people keep social timing that is significantly different to circadian timing, which dysregulates circadian rhythms. Several recent large cohort studies have found that greater degrees of social jetlag are significantly, inversely associated with rates of metabolic disease, in particular type-2 diabetes and obesity, associations which remain after controlling for variables like sleep duration and “chronotype” [whether someone is a morning type or evening type] [10][11].

In addition, both the duration and intensity of artificial light exposure at night are associated with metabolic dysfunction, obesity and abnormal lipid profiles [12][13]. One issue in relation to this observation is the indirect effect of extended evening wakefulness, which increases propensity for late-night eating, and late meal timing is associated with higher total daily calorie intake and increased BMI, independent of sleep timing and duration [14][15]. Nutrient utilisation and energy expenditure are regulated by the circadian system, and late-night eating alters the dichotomous feed/fast period and causes circadian rhythms in the digestive system, pancreas, liver, and other metabolic peripheral tissues to become offset from the central clock [16].

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