The human circadian system regulates hunger independently of behavioral factors, resulting in a trough in the biological morning and a peak in the biological evening. However, the role of the only ...known orexigenic hormone, ghrelin, in this circadian rhythm is unknown. Furthermore, although shift work is an obesity risk factor, the separate effects of the endogenous circadian system, the behavioral cycle, and circadian misalignment on ghrelin has not been systematically studied. Here we show-by using two 8-day laboratory protocols-that circulating active (acylated) ghrelin levels are significantly impacted by endogenous circadian phase in healthy adults. Active ghrelin levels were higher in the biological evening than the biological morning (fasting +15.1%, P = 0.0001; postprandial +10.4%, P = 0.0002), consistent with the circadian variation in hunger (P = 0.028). Moreover, circadian misalignment itself (12-h behavioral cycle inversion) increased postprandial active ghrelin levels (+5.4%; P = 0.04). While not significantly influencing hunger (P > 0.08), circadian misalignment increased appetite for energy-dense foods (all P < 0.05). Our results provide possible mechanisms for the endogenous circadian rhythm in hunger, as well as for the increased risk of obesity among shift workers.
Circadian clocks and insulin resistance Stenvers, Dirk Jan; Scheer, Frank A J L; Schrauwen, Patrick ...
Nature reviews. Endocrinology,
02/2019, Letnik:
15, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Insulin resistance is a main determinant in the development of type 2 diabetes mellitus and a major cause of morbidity and mortality. The circadian timing system consists of a central brain clock in ...the hypothalamic suprachiasmatic nucleus and various peripheral tissue clocks. The circadian timing system is responsible for the coordination of many daily processes, including the daily rhythm in human glucose metabolism. The central clock regulates food intake, energy expenditure and whole-body insulin sensitivity, and these actions are further fine-tuned by local peripheral clocks. For instance, the peripheral clock in the gut regulates glucose absorption, peripheral clocks in muscle, adipose tissue and liver regulate local insulin sensitivity, and the peripheral clock in the pancreas regulates insulin secretion. Misalignment between different components of the circadian timing system and daily rhythms of sleep-wake behaviour or food intake as a result of genetic, environmental or behavioural factors might be an important contributor to the development of insulin resistance. Specifically, clock gene mutations, exposure to artificial light-dark cycles, disturbed sleep, shift work and social jet lag are factors that might contribute to circadian disruption. Here, we review the physiological links between circadian clocks, glucose metabolism and insulin sensitivity, and present current evidence for a relationship between circadian disruption and insulin resistance. We conclude by proposing several strategies that aim to use chronobiological knowledge to improve human metabolic health.
Context:
Shift work is a risk factor for diabetes. The separate effects of the endogenous circadian system and circadian misalignment (ie, misalignment between the central circadian pacemaker and ...24-hour environmental/behavioral rhythms such as the light/dark and feeding/fasting cycles) on glucose tolerance in shift workers are unknown.
Objective:
The objective of the study was to test the hypothesis that the endogenous circadian system and circadian misalignment separately affect glucose tolerance in shift workers, both independently from behavioral cycle effects.
Design:
A randomized, crossover study with two 3-day laboratory visits.
Setting:
Center for Clinical Investigation at Brigham and Women's Hospital.
Patients:
Healthy chronic shift workers.
Intervention:
The intervention included simulated night work comprised of 12-hour inverted behavioral and environmental cycles (circadian misalignment) or simulated day work (circadian alignment).
Main Outcome Measures:
Postprandial glucose and insulin responses to identical meals given at 8:00 am and 8:00 pm in both protocols.
Results:
Postprandial glucose was 6.5% higher at 8:00 pm than 8:00 am (circadian phase effect), independent of behavioral effects (P = .0041). Circadian misalignment increased postprandial glucose by 5.6%, independent of behavioral and circadian effects (P = .0042). These variations in glucose tolerance appeared to be explained, at least in part, by different insulin mechanisms: during the biological evening by decreased pancreatic β-cell function (18% lower early and late phase insulin; both P ≤ .011) and during circadian misalignment presumably by decreased insulin sensitivity (elevated postprandial glucose despite 10% higher late phase insulin; P = .015) without change in early-phase insulin (P = .38).
Conclusions:
Internal circadian time affects glucose tolerance in shift workers. Separately, circadian misalignment reduces glucose tolerance in shift workers, providing a mechanism to help explain the increased diabetes risk in shift workers.
The circadian system serves one of the most fundamental properties present in nearly all organisms: it generates 24-h rhythms in behavioral and physiological processes and enables anticipating and ...adapting to daily environmental changes. Recent studies indicate that the circadian system is important in regulating the daily rhythm in glucose metabolism. Disturbance of this circadian control or of its coordination relative to the environmental/behavioral cycle, such as in shift work, eating late, or due to genetic changes, results in disturbed glucose control and increased type 2 diabetes risk. Therefore, an in-depth understanding of the mechanisms underlying glucose regulation by the circadian system and its disturbance may help in the development of therapeutic interventions against the deleterious health consequences of circadian disruption.
The circadian system generates endogenous rhythms of approximately 24 h, the synchronisation of which are vital for healthy bodily function. The timing of many physiological processes, including ...glucose metabolism, are coordinated by the circadian system, and circadian disruptions that desynchronise or misalign these rhythms can result in adverse health outcomes. In this review, we cover the role of the circadian system and its disruption in glucose metabolism in healthy individuals and individuals with type 2 diabetes mellitus. We begin by defining circadian rhythms and circadian disruption and then we provide an overview of circadian regulation of glucose metabolism. We next discuss the impact of circadian disruptions on glucose control and type 2 diabetes. Given the concurrent high prevalence of type 2 diabetes and circadian disruption, understanding the mechanisms underlying the impact of circadian disruption on glucose metabolism may aid in improving glycaemic control.
Timing of dietary intake may play a role in obesity. However, previous studies produced mixed findings possibly due to inconsistent approaches to characterize meal timing and not taking into account ...chronotype and macronutrients. To address the aforementioned limitations, we have defined meal timing relative to sleep/wake timing, investigated the relationship between meal timing and body mass index (BMI) dependent on chronotype, and examined the associations.
BMI, chronotype, and dietary intakes were measured in 872 middle-to-older-aged adults by six 24-h dietary recalls in 1 year. We defined four time windows of intake relative to sleep timing: morning (within 2 h after getting out of bed), night (within 2 h before bedtime), and two midday periods in between (split by the midpoint of the waking period).
A higher percent of total daily energy intake consumed during the morning window was associated with lower odds of being overweight or obese (odds ratio (95% confidence intervals), 0.53 (0.31, 0.89)). This association was stronger in people with an earlier chronotype (0.32 (0.16, 0.66)). A higher percent of total daily energy intake consumed during the night window was associated with higher odds of being overweight or obese (1.82 (1.07, 3.08)), particularly in people with a later chronotype (4.94 (1.61, 15.14)). These associations were stronger for the intakes of carbohydrates and protein than for fat intake.
Our study suggests that higher dietary consumption after waking up and lower consumption close to bedtime associate with lower BMI, but the relationship differs by chronotype. Furthermore, the data demonstrate a clear relationship between the timing of carbohydrate and protein intake and obesity. Our findings highlight the importance of considering timing of intake relative to sleep timing when studying the associations of meal timing with obesity and metabolic health.
Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers ...is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show—by using two 8-d laboratory protocols—that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure during wake periods (SBP, +1.6 mmHg; DBP, +1.4 mmHg). Circadian misalignment decreased wake cardiac vagal modulation by 8–15%, as determined by heart rate variability analysis, and decreased 24-h urinary epinephrine excretion rate by 7%, without a significant effect on 24-h urinary norepinephrine excretion rate. Circadian misalignment increased 24-h serum interleukin-6, C-reactive protein, resistin, and tumor necrosis factor-α levels by 3–29%. We demonstrate that circadian misalignment per se increases blood pressure and inflammatory markers. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk.
Shift work is associated with increased human operational errors, presumably due to the circadian timing system that inhibits optimal cognitive function during the night. Circadian misalignment, ...which is the misalignment between the circadian pacemaker and behavioral/environmental cycles, impairs cognitive performance in non-shift workers. However, it remains uncertain whether the adverse cognitive consequences of circadian misalignment are also observed in chronic shift workers. Thus, we investigated the effects of circadian misalignment on cognitive performance in chronic shift workers. Using a randomized, cross-over design that simulated day shift work (circadian alignment) and night shift work (circadian misalignment), we show that circadian misalignment increases cognitive vulnerability on sustained attention, information processing and visual-motor performance, particularly after more than 10 hours of scheduled wakefulness. Furthermore, their increased levels of subjective sleepiness and their decreased sleep efficiency were significantly associated with impaired sustained attention and visual-motor performance. Our data suggest that circadian misalignment dramatically deteriorates cognitive performance in chronic shift workers under circadian misalignment. This increased cognitive vulnerability may have important safety consequences, given the increasing number of nighttime jobs that crucially rely on the availability of cognitive resources.
Shift work increases the risk for human errors, such that drowsiness due to shift work has contributed to major industrial disasters, including Space Shuttle Challenger, Chernobyl and Alaska Oil ...Spill disasters, with extraordinary socio-economical costs. Overnight operations pose a challenge because our circadian biology inhibits cognitive performance at night. Yet how the circadian system modulates cognition over multiple days under realistic shift work conditions remains to be established. Importantly, because task-specific cognitive brain regions show different 24-h circadian dynamics, we hypothesize that circadian misalignment impacts cognition task-dependently. Using a biologically-driven paradigm mimicking night shift work, with a randomized, cross-over design, we show that misalignment between the circadian pacemaker and behavioral/environmental cycles increases cognitive vulnerability on sustained attention, cognitive throughput, information processing and visual-motor performance over multiple days, compared to circadian alignment (day shifts). Circadian misalignment effects are task-dependent: while they acutely impair sustained attention with recovery after 3-days, they progressively hinder daily learning. Individuals felt sleepier during circadian misalignment, but they did not rate their performance as worse. Furthermore, circadian misalignment effects on sustained attention depended on prior sleep history. Collectively, daily circadian misalignment may provide an important biological framework for developing countermeasures against adverse cognitive effects in shift workers.
There is emerging literature demonstrating a relationship between the timing of feeding and weight regulation in animals. However, whether the timing of food intake influences the success of a ...weight-loss diet in humans is unknown.
To evaluate the role of food timing in weight-loss effectiveness in a sample of 420 individuals who followed a 20-week weight-loss treatment.
Participants (49.5% female subjects; age (mean ± s.d.): 42 ± 11 years; BMI: 31.4 ± 5.4 kg m(-2)) were grouped in early eaters and late eaters, according to the timing of the main meal (lunch in this Mediterranean population). 51% of the subjects were early eaters and 49% were late eaters (lunch time before and after 1500 hours, respectively), energy intake and expenditure, appetite hormones, CLOCK genotype, sleep duration and chronotype were studied.
Late lunch eaters lost less weight and displayed a slower weight-loss rate during the 20 weeks of treatment than early eaters (P=0.002). Surprisingly, energy intake, dietary composition, estimated energy expenditure, appetite hormones and sleep duration was similar between both groups. Nevertheless, late eaters were more evening types, had less energetic breakfasts and skipped breakfast more frequently that early eaters (all; P<0.05). CLOCK rs4580704 single nucleotide polymorphism (SNP) associated with the timing of the main meal (P=0.015) with a higher frequency of minor allele (C) carriers among the late eaters (P=0.041). Neither sleep duration, nor CLOCK SNPs or morning/evening chronotype was independently associated with weight loss (all; P>0.05).
Eating late may influence the success of weight-loss therapy. Novel therapeutic strategies should incorporate not only the caloric intake and macronutrient distribution - as is classically done - but also the timing of food.
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