Alteration of circadian time structure of blood pressure caused by night shift schedule

The effects of night shift schedules on circadian time structure of blood pressure were studied in seven healthy young subjects by continuous monitoring of blood pressure every 30 min for 72 h. In the control experiment, subjects were instructed to sleep at regular times with the light off at 00.00 h and the light on at 07.00 h. In the shift experiment, they were instructed to go to bed at 06.00 h and wake up at 11.00 h. The circadian rhythm of blood pressure rapidly phase delayed by 3.5 h in the second night shift day as a group phenomenon. Individual differences in changes in power spectral patterns of blood pressure were found in the night shift schedule. Ultradian rhythmicity of blood pressure was more pronounced in three subjects, whereas the circadian rhythmicity was maintained in four subjects. These findings held when the adaptation to shift work was taken into account.     

The Effects of Shift Work on Cardio-Metabolic Diseases and Eating Patterns

Energy metabolism is tightly linked with circadian rhythms, exposure to ambient light, sleep/wake, fasting/eating, and rest/activity cycles. External factors, such as shift work, lead to a disruption of these rhythms, often called circadian misalignment. Circadian misalignment has an impact on some physiological markers. However, these proxy measurements do not immediately translate into major clinical health outcomes, as shown by later detrimental health effects of shift work and cardio-metabolic disorders. This review focuses on the effects of shift work on circadian rhythms and its implications in cardio-metabolic disorders and eating patterns. Shift work appears to be a risk factor of overweight, obesity, type 2 diabetes, elevated blood pressure, and the metabolic syndrome. However, past studies showed discordant findings regarding the changes of lipid profile and eating patterns. Most studies were either small and short lab studies, or bigger and longer cohort studies, which could not measure health outcomes in a detailed manner. These two designs explain the heterogeneity of shift schedules, occupations, sample size, and methods across studies. Given the burden of non-communicable diseases and the growing concerns about shift workers’ health, novel approaches to study shift work in real contexts are needed and would allow a better understanding of the interlocked risk factors and potential mechanisms involved in the onset of metabolic disorders.     

Diurnal variations of blood pressure in shift workers during day and night shifts

Summary The dependence of blood pressure upon internal rhythms and the short-term effects of shift rota on the blood pressure were investigated in shift workers. Blood pressure was measured every 30 min using automatic recorders for 24 h in 17 physically working men in a chemical factory during their morning and night shifts. Mean 24-h blood pressures were identical in the morning and night shifts. There were no differences of the mean blood pressure between the respective sleeping phases or between the working periods. The amplitudes of circadian blood pressure variations were equal. There was a phase difference of 8 h corresponding to the lag between the working periods. At this 8-h lag the hourly means of the 24-h blood pressure were closely correlated (r = 0.69). Comparisons of 24-h blood pressure profiles during the first and last days of a night shift week showed that the effects of night work on the blood pressure were already fully developed within the first 24h (r = 0.86). Thus the diurnal variations of the blood pressure are determined by the working and sleeping periods and largely independent of endogenous rhythm. There is no short-term alteration of the mean 24-h blood pressure after shift rota.     

The role of the circadian clock system in nutrition and metabolism

Mammals have an endogenous timing system in the suprachiasmatic nuclei (SCN) of the hypothalamic region of the brain. This internal clock system is composed of an intracellular feedback loop that drives the expression of molecular components and their constitutive protein products to oscillate over a period of about 24?h (hence the term 'circadian'). These circadian oscillations bring about rhythmic changes in downstream molecular pathways and physiological processes such as those involved in nutrition and metabolism. It is now emerging that the molecular components of the clock system are also found within the cells of peripheral tissues, including the gastrointestinal tract, liver and pancreas. The present review examines their role in regulating nutritional and metabolic processes. In turn, metabolic status and feeding cycles are able to feed back onto the circadian clock in the SCN and in peripheral tissues. This feedback mechanism maintains the integrity and temporal coordination between various components of the circadian clock system. Thus, alterations in environmental cues could disrupt normal clock function, which may have profound effects on the health and well-being of an individual.     

Beneficial Effects of Early Time-Restricted Feeding on Metabolic Diseases: Importance of Aligning Food Habits with the Circadian Clock

The importance of metabolic health is a major societal concern due to the increasing prevalence of metabolic diseases such as obesity, diabetes, and various cardiovascular diseases. The circadian clock is clearly implicated in the development of these metabolic diseases. Indeed, it regulates physiological processes by hormone modulation, thus helping the body to perform them at the ideal time of day. Since the industrial revolution, the actions and rhythms of everyday life have been modified and are characterized by changes in sleep pattern, work schedules, and eating habits. These modifications have in turn lead to night shift, social jetlag, late-night eating, and meal skipping, a group of customs that causes circadian rhythm disruption and leads to an increase in metabolic risks. Intermittent fasting, especially the time-restricted eating, proposes a solution: restraining the feeding window from 6 to 10 h per day to match it with the circadian clock. This approach seems to improve metabolic health markers and could be a therapeutic solution to fight against metabolic diseases. This review summarizes the importance of matching life habits with circadian rhythms for metabolic health and assesses the advantages and limits of the application of time-restricted fasting with the objective of treating and preventing metabolic diseases.     

Chronobiology and Obesity: Interactions between Circadian Rhythms and Energy Regulation

Recent advances in the understanding of the molecular, genetic, neural, and physiologic basis for the generation and organization of circadian clocks in mammals have revealed profound bidirectional interactions between the circadian clock system and pathways critical for the regulation of metabolism and energy balance. The discovery that mice harboring a mutation in the core circadian gene circadian locomotor output cycles kaput (Clock) develop obesity and evidence of the metabolic syndrome represented a seminal moment for the field, clearly establishing a link between circadian rhythms, energy balance, and metabolism at the genetic level. Subsequent studies have characterized in great detail the depth and magnitude of the circadian clock’s crucial role in regulating body weight and other metabolic processes. Dietary nutrients have been shown to influence circadian rhythms at both molecular and behavioral levels; and many nuclear hormone receptors, which bind nutrients as well as other circulating ligands, have been observed to exhibit robust circadian rhythms of expression in peripheral metabolic tissues. Furthermore, the daily timing of food intake has itself been shown to affect body weight regulation in mammals, likely through, at least in part, regulation of the temporal expression patterns of metabolic genes. Taken together, these and other related findings have transformed our understanding of the important role of time, on a 24-h scale, in the complex physiologic processes of energy balance and coordinated regulation of metabolism. This research has implications for human metabolic disease and may provide unique and novel insights into the development of new therapeutic strategies to control and combat the epidemic of obesity.     

Circadian Rhythms,Metabolism, and Chrononutrition in Rodents and Humans

Chrononutrition is an emerging discipline that builds on the intimate relation between endogenous circadian (24-h) rhythms and metabolism. Circadian regulation of metabolic function can be observed from the level of intracellular biochemistry to whole-organism physiology and even postprandial responses. Recent work has elucidated the metabolic roles of circadian clocks in key metabolic tissues, including liver, pancreas, white adipose, and skeletal muscle. For example, tissue-specific clock disruption in a single peripheral organ can cause obesity or disruption of whole-organism glucose homeostasis. This review explains mechanistic insights gained from transgenic animal studies and how these data are being translated into the study of human genetics and physiology. The principles of chrononutrition have already been demonstrated to improve human weight loss and are likely to benefit the health of individuals with metabolic disease, as well as of the general population.     

Postnatal ontogenesis of clock genes in mouse suprachiasmatic nucleus and heart

Background  

The master clock within the hypothalamic suprachiasmatic nucleus (SCN) synchronizing clocks in peripheral tissues is entrained by the environmental condition, such as the light-dark (LD) cycle. The mechanisms of circadian clockwork are similar in both SCN and peripheral tissues. The aim of the present work was to observe the profiles of clock genes expression in mouse central and peripheral tissues within postnatal day 5 (P5). The daily expression of four clock genes mRNA (Bmal1, Per2, Cry1 and Rev-erb alpha) in mouse SCN and heart was measured at P1, P3 and P5 by real-time PCR.     

Impact of Time-Restricted Feeding on Adaptation to a 6-Hour Delay Phase Shift or a 12-Hour Phase Shift in Mice

Nowadays, more and more people are suffering from circadian disruption. However, there is no well-accepted treatment. Recently, time-restricted feeding (TRF) was proposed as a potential non-drug intervention to alleviate jet lag in mice, especially in mice treated with a 6-h advanced phase shift. Here, we challenged C57BL/6 mice with a 6-h delay phase shift or a 12-h shift (day-night reversal) combined with 6- or 12-h TRF within the dark phase and found the beneficial effects of given TRF strategies in certain phase-shifting situations. Although behavioral fitness did not correlate well with health status, none of the TRF strategies we used deteriorated lipopolysaccharide-induced sepsis. These findings improve our understanding of the benefits of TRF for adaptation to circadian disruption.     

Circadian rhythms and their application to occupational health and medicine

Detailed measurements of many physiological variables over the course of 24h have indicated that normal human subjects show circadian rhythms. Such rhythmicity derives from an internal clock as well as our rhythmic environment and rhythmic habits. The internal clock is normally adjusted to run with an exact 24-h period by the rhythmic influences in the environment so that, in health, there is a synchrony between the different body rhythms, the internal clock and the external clock. There is evidence that in some individuals such a 'matching' of rhythms does not occur. Further, abnormalities are imposed upon this system after time-zone transition and during irregular hours of work (including night work). In all cases, undesirable side-effects are evident in the individual concerned. Where possible, an explanation of these problems is given together with advice that might help to ameliorate them. When applications to medicine are considered, a knowledge of normal circadian rhythmicity can be a diagnostic aid and can, in addition, indicate the most appropriate time for replacement therapy. It is also apparent that the efficacy of drugs can depend upon their time of administration. These aspects of chronopharmacology have most application in the treatment of asthma, arthritis and cancer, all of which are considered in some detail.     

Does a high-fat diet affect the circadian clock,or is it the other way around? A systematic review

This paper reviews studies that addressed the influence of diet on circadian rhythmicity in mice and, in turn, circadian clock chronodisruption and its role in the development of metabolic disorders. Studies from the past 14 years were selected via a systematic search conducted using the PubMed electronic database. After applying the inclusion and exclusion criteria, 291 studies were selected, of which 13 were chosen using the following inclusion criteria: use of a high-fat diet for mice, evaluation of clock gene expression, and the association between chronodisruption and lipid metabolism disorders. These studies reported changes in animals' biological clock when they developed metabolic disorders by consuming a high-fat diet. It was also evident that some clock gene mutations or deletions triggered metabolic changes. Disturbances of clock gene machinery may play important roles in lipid metabolism and the development of atherosclerotic processes. However, many metabolic processes also affect the function of clock genes and circadian systems. In summary, this review's results may provide new insights into the reciprocal regulation of energy homeostasis and the biological clock.     

婴儿24小时生理节奏的发育

近年来研究指出生物钟的时间系统发育始于胎儿。生物钟位于视交叉上核 ,在灵长目中 ,其发育始于妊中期。灵长目婴儿的生理节律对光的应答出现在相当早的阶段。低强度光能调节生物钟的发育。出生后生物节律系统继续成熟着 ,至 2个月时 ,明显地呈现睡眠 觉醒和激素分泌的生理性节律。光调节生物钟的时间对婴儿来说是很重要的。早产儿暴露在周期性低强度光环境中导致休息和活动方式与 2 4小时昼夜节律的同步。对婴儿 2 4小时生理节律发育的关注在促进新生儿保健中具有非常重要的作用     

In time for Beijing: influence of the biological clock on athletic performance

Circadian rhythms are a common characteristic ofmulticellular organisms and evolved as an adaptation to the earth's rotation on its axis. In humans, circadian rhythms are regulated by suprachiasmatic nuclei located at the base of the hypothalamus. The suprachiasmatic nuclei function as a biological clock that controls the daily rhythms of nearly all physiological functions. External light synchronises the endogenous clock to the environmental light-dark cycle. When travelling rapidly across multiple time zones, the endogenous clock must adjust to the new time. During the period of adjustment, many physiological circadian rhythms become desynchronised and jet lag occurs. Few studies have analysed the influence of jet lag on athletic performance. These studies indicate that performance levels can decline during jet lag. This seems to be a result of the desynchronized physiological state and sleep disturbances, leading to suboptimal values of blood pressure, heart rate, body temperature, and muscle strength. We give some advice for athletes who must cross multiple time zones shortly before a competition.     

Time-place learning is altered by perinatal low-protein malnutrition in the adult rat

Malnutrition produces changes in the central nervous system (CNS) of mammals during development, related to the intensity and timing of the malnutrition insult during the pre- or postnatal period. Protein malnutrition produces irreversible changes in hippocampal formation and some brain stem nuclei. The suprachiasmatic nucleus (SCN) is dramatically altered by low-protein diets during the gestational and perinatal periods. Also, it is known that circadian oscillators regulate physiological, behavioral, and cognitive processes and there is evidence that the time-place learning process exhibits a daily temporal distribution. The aim of this study was to determine the effects of chronic, prenatal, or postnatal malnutrition on daily patterns of the time-place learning process in the adult rat. Forty Sprague-Dawley male 90-day-old rats, were divided into four groups: 10 well nourished controls (Co), 10 chronically (CM), 10 prenatally malnourished (PrM), and 10 postnatally malnourished (PtM) rats. Efficiency in time-place learning was tested by using a behavioral T-maze. Each rat was assayed for 10 trials before considering the final probe of efficiency. Each trial was 60 seconds long, final efficiency was measured by the amount of time the rat took to reach the end of an arm containing a water pot. Each rat was tested in 2-hour spans until completion of a full 24-hour cycle. A Cosinor analysis was used to evaluate acrophase and percentage of rhythmicity. The obtained results suggest that time-place learning process is influenced by the circadian clock. The severity and timing of prenatal or chronic protein malnutrition modifies the acrophase and rhythmicity of the learning circadian pattern, which can impact important cognitive functions.     

Severe impairment of circadian rhythm in Alzheimer’s disease

Circadian rhythmicity was repeatedly determined in a patient with Alzheimer??s disease by measuring his core temperature with a rectal thermistor and motor activity by an ambulatory activity monitor. The first recording, performed 9 years after he was diagnosed with Alzheimer??s disease, showed well organized 24 hr circadian rhythm of core body temperature. The second recording, made four months later, showed very poor fit of core body temperature to 24 hour rhythm, but excellent fit with 36 hour rhythm. The third recording, made two months later, showed again good fit of core body temperature with 24 hour cycle. The last recording, which was performed 5 months later, showed almost complete disappearance of circadian rhythm of body temperature. These changes probably reflect gradual lengthening of the circadian cycle that at one point became extremely lengthened before returning to the 24 hr cycle.     

Metabolic responses to nocturnal eating in men are affected by sources of dietary energy

Because night work is becoming more prevalent, we studied whether feeding at different times of a 24-h period would elicit different metabolic responses and whether dietary macronutrient composition would affect these responses. Seven men (26-43 y, 19.9-26.6 kg/m(2)) consumed two isocaloric diets, in a crossover design. The diets were a high carbohydrate (HC) diet [65 energy % (E%) carbohydrates, 20E% fat] and a high fat (HF) diet (40E% carbohydrates, 45E% fat). After a 6-d diet-adjustment period, the men were kept awake for 24 h and the food (continuation of respective diet) was provided as six isocaloric meals (i.e., every 4 h). Energy and substrate turnover, heart rate, mean arterial pressure (MAP), blood glucose, triacylglycerol (TAG), nonesterified fatty acid (NEFA) and glycerol were measured throughout the 24-h period. Significantly higher energy expenditure and NEFA concentration, and lower blood glucose and TAG concentrations were observed when the men consumed the HF diet than when they consumed the HC diet. Significant circadian patterns were seen in body and skin temperature (nadir, 0400-0500 h). When the men consumed the HF diet, significant circadian patterns were seen in fat oxidation (nadir, 0800-1200 h; plateau, 1200-0800 h), heat release (nadir, 0800-1200 h; plateau, 1600-0800 h), heart rate (nadir, 0000 h), blood glucose (nadir, 0800-1200 h; peak, 0000-0400 h), NEFA (nadir, 0800-1200 h; peak, 1200-2000 h) and TAG (nadir, 0800-1200 h; peak, 0400-0800 h) concentrations. Energy expenditure, carbohydrate oxidation, MAP and glycerol concentration did not display circadian patterns. Unequal variances eradicated most circadian effects in the HC-diet data. The increased TAG concentration in response to feeding at 0400 h might be involved in the higher TAG concentrations seen in shift workers. Distinct macronutrient/circadian-dependent postprandial responses were seen in most studied variables.     

Gastrointestinal Vagal Afferents and Food Intake: Relevance of Circadian Rhythms

Gastrointestinal vagal afferents (VAs) play an important role in food intake regulation, providing the brain with information on the amount and nutrient composition of a meal. This is processed, eventually leading to meal termination. The response of gastric VAs, to food-related stimuli, is under circadian control and fluctuates depending on the time of day. These rhythms are highly correlated with meal size, with a nadir in VA sensitivity and increase in meal size during the dark phase and a peak in sensitivity and decrease in meal size during the light phase in mice. These rhythms are disrupted in diet-induced obesity and simulated shift work conditions and associated with disrupted food intake patterns. In diet-induced obesity the dampened responses during the light phase are not simply reversed by reverting back to a normal diet. However, time restricted feeding prevents loss of diurnal rhythms in VA signalling in high fat diet-fed mice and, therefore, provides a potential strategy to reset diurnal rhythms in VA signalling to a pre-obese phenotype. This review discusses the role of the circadian system in the regulation of gastrointestinal VA signals and the impact of factors, such as diet-induced obesity and shift work, on these rhythms.     

Subjective wellbeing of shift workers in relation to individual characteristics of circadian rhythm

With a goal to test the influence of individual traits of circadian rhythms on the tolerance of shiftwork a circadian questionnaire has been developed with the method of factors analysis. There are two scales in the final form of the questionnaire representing two chronobiological characteristics: morningness - eveningsness (circadian phase-position) and flexibility of the sleep-wake-rhythm. Sex- and age-norms exist for the two scales. Reliability and validity have been demonstrated. The results of an epidemiological study shows that the hypothesis of better adjustment to shiftwork of evening-types can not be verified. A better predictor of tolerance to shift work in terms of wellbeing seems to be the individual circadian trait flexibility of sleep-wake-rhythm.     

Melatonin Levels in Children with Obesity Are Associated with Metabolic Risk and Inflammatory Parameters

Melatonin, the hormone of circadian rhythm regulation, is involved in the modulation of mitochondrial activity through its antioxidant and anti-inflammatory properties. Alteration of circadian rhythms such as sleep is related to obesity and metabolic pathogenesis in adulthood, but studies during childhood are scarce. The present study investigated the association of melatonin with metabolic and inflammatory markers in children with (n = 113) and without obesity (n = 117). Melatonin was measured in saliva four and two hours before bedtime, and after one hour of sleep. Cardiometabolic factors, high sensitivity C-reactive protein, immune markers (monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, tumor necrosis α and interferon-γ), leptin and ghrelin were determined. Sleep duration was recorded by a questionnaire. The melatonin level at 1 h after sleep was found to be increased more than twofold in children with obesity (90.16 (57.16–129.16) pg/mL) compared to controls (29.82 (19.05–61.54) pg/mL, p < 0.001) and was related to fat mass (rho = 0.294, p < 0.001); melatonin levels at 1 h after sleep were inversely correlated with high-density lipoprotein cholesterol. Positive correlation was found with apolipoprotein B, adipokines, high sensitivity C-reactive protein, plasminogen activator inhibitor-1 and tumor necrosis factor-α. Shorter sleep duration and earlier waking times were recorded in children with obesity. In conclusion, melatonin in children with obesity appears to be involved in the global metabolic and inflammatory alteration of this condition.     

Physiological and pathophysiological role of the circadian clock system

It has been well known for ages that in living organisms the rhythmicity of biological processes is linked to the ~ 24-hour light-dark cycle. However, the exact function of the circadian clock system has been explored only in the past decades. It came to light that the photosensitive primary "master clock" is situated in the suprachiasmatic photosensitive nuclei of the special hypothalamic region, and that it is working according to ~24-hour changes of light and darkness. The master clock sends its messages to the peripheral "slave clocks". In many organs, like pancreatic β-cells, the slave clocks have autonomic functions as well. Two essential components of the clock system are proteins encoded by the CLOCK and BMAL1 genes. CLOCK genes are in interaction with endonuclear receptors such as peroxisoma-proliferator activated receptors and Rev-erb-α, as well as with the hypothalamic-pituitary-adrenal axis, regulating the adaptation to stressors, energy supply, metabolic processes and cardiovascular system. Melatonin, the product of corpus pineale has a significant role in the functions of the clock system. The detailed discovery of the clock system has changed our previous knowledge about the development of many diseases. The most explored fields are hypertension, cardiovascular diseases, metabolic processes, mental disorders, cancers, sleep apnoe and joint disorders. CLOCK genes influence ageing as well. The recognition of the periodicity of biological processes makes the optimal dosing of certain drugs feasible. The more detailed discovery of the interaction of the clock system might further improve treatment and prevention of many disorders.