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The Circadian Syndrome: is the Metabolic Syndrome and much more!
Zimmet, P, Alberti, KGMM, Stern, N, Bilu, C, El-Osta, A, Einat, H, Kronfeld-Schor, N
Journal of internal medicine. 2019;(2):181-191
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Abstract
The Metabolic Syndrome is a cluster of cardio-metabolic risk factors and comorbidities conveying high risk of both cardiovascular disease and type 2 diabetes. It is responsible for huge socio-economic costs with its resulting morbidity and mortality in most countries. The underlying aetiology of this clustering has been the subject of much debate. More recently, significant interest has focussed on the involvement of the circadian system, a major regulator of almost every aspect of human health and metabolism. The Circadian Syndrome has now been implicated in several chronic diseases including type 2 diabetes and cardiovascular disease. There is now increasing evidence connecting disturbances in circadian rhythm with not only the key components of the Metabolic Syndrome but also its main comorbidities including sleep disturbances, depression, steatohepatitis and cognitive dysfunction. Based on this, we now propose that circadian disruption may be an important underlying aetiological factor for the Metabolic Syndrome and we suggest that it be renamed the 'Circadian Syndrome'. With the increased recognition of the 'Circadian Syndrome', circadian medicine, through the timing of exercise, light exposure, food consumption, dispensing of medications and sleep, is likely to play a much greater role in the maintenance of both individual and population health in the future.
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Focusing on the nuclear and subnuclear dynamics of light and circadian signalling.
Ronald, J, Davis, SJ
Plant, cell & environment. 2019;(10):2871-2884
Abstract
Circadian clocks provide organisms the ability to synchronize their internal physiological responses with the external environment. This process, termed entrainment, occurs through the perception of internal and external stimuli. As with other organisms, in plants, the perception of light is a critical for the entrainment and sustainment of circadian rhythms. Red, blue, far-red, and UV-B light are perceived by the oscillator through the activity of photoreceptors. Four classes of photoreceptors signal to the oscillator: phytochromes, cryptochromes, UVR8, and LOV-KELCH domain proteins. In most cases, these photoreceptors localize to the nucleus in response to light and can associate to subnuclear structures to initiate downstream signalling. In this review, we will highlight the recent advances made in understanding the mechanisms facilitating the nuclear and subnuclear localization of photoreceptors and the role these subnuclear bodies have in photoreceptor signalling, including to the oscillator. We will also highlight recent progress that has been made in understanding the regulation of the nuclear and subnuclear localization of components of the plant circadian clock.
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Clocking In, Working Out: Circadian Regulation of Exercise Physiology.
Duglan, D, Lamia, KA
Trends in endocrinology and metabolism: TEM. 2019;(6):347-356
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Abstract
Research over the past century indicates that the daily timing of physical activity impacts on both immediate performance and long-term training efficacy. Recently, several molecular connections between circadian clocks and exercise physiology have been identified. Circadian clocks are protein-based oscillators that enable anticipation of daily environmental cycles. Cell-autonomous clocks are present in almost all cells of the body, and their timing is set by a variety of internal and external signals, including hormones and dietary intake. Improved understanding of the relationship between molecular clocks and exercise will benefit professional athletes and public health guidelines for the general population. We discuss here the role of circadian clocks in exercise, and explore time-of-day effects and the proposed molecular and physiological mechanisms.
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Circadian rhythms and exercise - re-setting the clock in metabolic disease.
Gabriel, BM, Zierath, JR
Nature reviews. Endocrinology. 2019;(4):197-206
Abstract
Perturbed diurnal rhythms are becoming increasingly evident as deleterious events in the pathology of metabolic diseases. Exercise is well characterized as a crucial intervention in the prevention and treatment of individuals with metabolic diseases. Little is known, however, regarding optimizing the timing of exercise bouts in order to maximize their health benefits. Furthermore, exercise is a potent modulator of skeletal muscle metabolism, and it is clear that skeletal muscle has a strong circadian profile. In humans, mitochondrial function peaks in the late afternoon, and the circadian clock might be inherently impaired in myotubes from patients with metabolic disease. Timing exercise bouts to coordinate with an individual's circadian rhythms might be an efficacious strategy to optimize the health benefits of exercise. The role of exercise as a Zeitgeber can also be used as a tool in combating metabolic disease. Shift work is known to induce acute insulin resistance, and appropriately timed exercise might improve health markers in shift workers who are at risk of metabolic disease. In this Review, we discuss the literature regarding diurnal skeletal muscle metabolism and the interaction with exercise bouts at different times of the day to combat metabolic disease.
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Retrograde signalling as an informant of circadian timing.
Jones, MA
The New phytologist. 2019;(4):1749-1753
Abstract
Contents Summary 1749 I. The circadian system is responsive to environmental change 1749 II. Photoassimilates regulate circadian timing 1750 III. Retrograde signals contribute to circadian timing 1750 IV. Conclusions 1752 Acknowledgements 1752 References 1752 SUMMARY The circadian system comprises interlocking transcriptional-translational feedback loops that regulate gene expression and consequently modulate plant development and physiology. In order to maximize utility, the circadian system is entrained by changes in temperature and light, allowing endogenous rhythms to be synchronized with both daily and seasonal environmental change. Although a great deal of environmental information is decoded by a suite of photoreceptors, it is also becoming apparent that changes in cellular metabolism also contribute to circadian timing, through either the stimulation of metabolic pathways or the accumulation of metabolic intermediates as a consequence of environmental stress. As the source of many of these metabolic byproducts, mitochondria and chloroplasts have begun to be viewed as environmental sensors, and rapid advancement of this field is revealing the complex web of signalling pathways initiated by organelle perturbation. This review highlights recent advances in our understanding of how this metabolic regulation influences circadian timing.
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Chronopathophysiological implications of orexin in sleep disturbances and lifestyle-related disorders.
Tsuneki, H, Wada, T, Sasaoka, T
Pharmacology & therapeutics. 2018;:25-44
Abstract
Sleep, a mysterious behavior, has recently been recognized as a crucial factor for health and longevity. The daily sleep/wake cycle provides the basis of biorhythms controlling whole-body homeostasis and homeodynamics; therefore, disruption of sleep causes several physical and psychological disorders, including cardiovascular disease, obesity, diabetes, cancer, anxiety, depression, and cognitive dysfunction. However, the mechanism linking sleep disturbances and sleep-related disorders remains unknown. Orexin (also known as hypocretin) is a neuropeptide produced in the hypothalamus. Central levels of orexin oscillate with the daily rhythm and peak at the awake phase. Orexin plays a major role in stabilizing the wakefulness state. Orexin deficiency causes sleep/wake-state instability, resulting in narcolepsy. Hyper-activation of the orexin system also causes sleep disturbances, such as insomnia, and hence, suvorexant, an orexin receptor antagonist, has been clinically used to treat insomnia. Importantly, central actions of orexin regulate motivated behaviors, stress response, and energy/glucose metabolism by coordinating the central-autonomic nervous systems and endocrine systems. These multiple actions of orexin maintain survival. However, it remains unknown whether chronopharmacological interventions targeting the orexin system ameliorate sleep-related disorders as well as sleep in humans. To understand the significance of adequate orexin action for prevention of these disorders, this review summarizes the physiological functions of daily orexin action and pathological implications of its mistimed or reduced action in sleep disturbances and sleep-related disorders (lifestyle-related physical and neurological disorders in particular). Timed administration of drugs targeting the orexin system may prevent lifestyle-related diseases by improving the quality of life in patients with sleep disturbances.
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Links between the circadian rhythm, obesity and the microbiome.
Rácz, B, Dušková, M, Stárka, L, Hainer, V, Kunešová, M
Physiological research. 2018;(Suppl 3):S409-S420
Abstract
Obesity is linked to a wide range of serious illnesses. In addition to the important impact on the health of the individual, obesity also has a substantial impact on the economy. Disruption of physiological day-night cycles could contribute to the increased incidence of obesity. According to the American National Sleep Federation, the percentage of the people who reported a sleep duration of six hours or less increased from 12 to 37 % over ten years. Insufficient sleep leads not only to an increase of the total calorie intake but changes the meal preference in favor of palatable foods and meals with high carbohydrate content. A decrease of leptin and increase of ghrelin levels caused by sleep deficiency can also play a role. In addition to the higher caloric intake, the timing of food consumption should be taken into account. The same meal eaten during the night versus the day is associated with increased postprandial glucose and triglyceride levels. The gut microbiome has also been recently understood as an endocrine system, with links between the gut microbiome and circadian rhythm changes possibly influencing increased obesity.
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[Thermal and Lighting Housing Environments and Circadian Blood Pressure Variability: Findings from the HEIJO-KYO Cohort].
Obayashi, K, Saeki, K
Nihon eiseigaku zasshi. Japanese journal of hygiene. 2018;(2):138-142
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Abstract
The purpose of this short review is to describe the influence of housing environment temperature and lighting on circadian blood pressure (BP) variability using data from the HEIJO-KYO cohort, a community-based cohort study launched in 2010. Increased excess mortality from cardiovascular disease in winter is a worldwide problem. Previous studies showed higher conventional BP and higher daytime ambulatory BP in winter; however, the relationship between indoor cold exposure and circadian BP variability remained unknown. In our cohort, we found a significant inverse relationship between indoor temperature and morning BP surge, independent of potential confounding factors. In addition, we found the tertile group with the lowest daytime indoor temperatures showed significantly higher urinary sodium excretion than the tertile group with the highest daytime indoor temperatures. Higher sodium intake caused by indoor cold exposure may partly explain the higher BP in winter. Physiologically, light exposure is the most important environmental cue for the circadian timing system and melatonin secretion. In our cohort, we observed that an increase in nighttime short-wave length light exposure and a decrease in daytime light exposure were significantly associated with lower melatonin secretion. Furthermore, lower melatonin levels were significantly related to higher nighttime BPs and parameters of atherosclerosis, which are predictors of cardiovascular disease incidence. Further longitudinal studies of the influence of housing environment temperature and lighting on cardiovascular disease incidence are required.
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Sleep in Normal Aging.
Li, J, Vitiello, MV, Gooneratne, NS
Sleep medicine clinics. 2018;(1):1-11
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Abstract
Sleep patterns change with aging, independent of other factors, and include advanced sleep timing, shortened nocturnal sleep duration, increased frequency of daytime naps, increased number of nocturnal awakenings and time spent awake during the night, and decreased slow wave sleep. Most of these changes seem to occur between young and middle adulthood; sleep parameters remain largely unchanged among healthy older adults. The circadian system and sleep homeostatic mechanisms become less robust with normal aging. The amount and pattern of sleep-related hormone secretion change as well. The causes of sleep disturbances in older adults are multifactorial.
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The effect of intermittent fasting during Ramadan on sleep, sleepiness, cognitive function, and circadian rhythm.
Qasrawi, SO, Pandi-Perumal, SR, BaHammam, AS
Sleep & breathing = Schlaf & Atmung. 2017;(3):577-586
Abstract
PURPOSE Studies have shown that experimental fasting can affect cognitive function, sleep, and wakefulness patterns. However, the effects of experimental fasting cannot be generalized to fasting during Ramadan due to its unique characteristics. Therefore, there has been increased interest in studying the effects of fasting during Ramadan on sleep patterns, daytime sleepiness, cognitive function, sleep architecture, and circadian rhythm. METHOD In this review, we critically discuss the current research findings in those areas during the month of Ramadan. RESULTS Available data that controlled for sleep/wake schedule, sleep duration, light exposure, and energy expenditure do not support the notion that Ramadan intermittent fasting increases daytime sleepiness and alters cognitive function. Additionally, recent well-designed studies showed no effect of fasting on circadian rhythms. However, in non-constrained environments that do not control for lifestyle changes, studies have demonstrated sudden and significant delays in bedtime and wake time. CONCLUSIONS Studies that controlled for environmental factors and sleep/wake schedule reported no significant disturbances in sleep architecture. Nevertheless, several studies have consistently reported that the main change in sleep architecture during fasting is a reduction in the proportion of REM sleep.