Project description:Misalignment of the endogenous circadian timing system leads to disruption of physiological rhythms and may contribute to the development of the deleterious health effects associated with night shift work. However, the molecular underpinnings remain to be elucidated. Here, we investigated the effect of a 4-day simulated night shift work protocol on the circadian regulation of the human transcriptome. Repeated blood samples were collected over two 24-hour measurement periods from eight healthy subjects under highly controlled laboratory conditions before and 4 days after a 10-hour delay of their habitual sleep period. RNA was extracted from peripheral blood mononuclear cells to obtain transcriptomic data. Cosinor analysis revealed a marked reduction of significantly rhythmic transcripts in the night shift condition compared with baseline at group and individual levels. Subsequent analysis using a mixed-effects model selection approach indicated that this decrease is mainly due to dampened rhythms rather than to a complete loss of rhythmicity: 73% of transcripts rhythmically expressed at baseline remained rhythmic during the night shift condition with a similar phase relative to habitual bedtimes, but with lower amplitudes. Functional analysis revealed that key biological processes are affected by the night shift protocol, most notably the natural killer cell-mediated immune response and Jun/AP1 and STAT pathways. These results show that 4 days of simulated night shifts leads to a loss in temporal coordination between the human circadian transcriptome and the external environment and impacts biological processes related to the adverse health effects associated to night shift work.
Project description:Night work has become necessary in our modern society. However, sleep deprivation induces a circadian misalignment that effectively contributes to the development of diseases associated with metabolic syndrome, such as obesity and diabetes. Here, we evaluated the pattern of circadian clock genes and endoplasmic reticulum stress (ERS) genes in addition to metabolic and anthropometric measures in subjects that work during a nocturnal period compared with day workers. We study 20 night workers (NW) and 20 day workers (DW) submitted to a work schedule of 12 h of work for 36 h of rest for at least 5 years in a hospital. The present report shows that NW have increased fasting blood glucose, glycated hemoglobin (HbA1c), triglycerides, and low-density lipoprotein (LDL)-cholesterol levels, and lower high-density lipoprotein (HDL)-cholesterol levels compared to DW. In addition, we observed that waist circumference (WC), waist-hip ratio (WHR), and systemic blood pressure are also increased in NW. Interestingly, gene expression analysis showed changes in CLOCK gene expression in peripheral blood mononuclear cells (PBMC) samples of NW compared to the DW, evidencing a peripheral circadian misalignment. This metabolic adaptation was accompanied by the up-regulation of many genes of ERS in NW. These findings support the hypothesis that night shift work results in disturbed glycemic and lipid control and affects the circadian cycle through the deregulation of peripheral CLOCK genes, which is possibly due to the activation of ERS. Thus, night work induces important metabolic changes that increase the risk of developing metabolic syndrome.
Project description:Misalignment of the daily sleep-wake and fasting-feeding cycles with the endogenous circadian timing system is an inevitable consequence of night shift work and is associated with adverse metabolic health effects. However, a detailed characterisation of the effects of night shifts on 24-h rhythms in the metabolome is missing. We performed targeted metabolomic profiling on plasma samples collected every 2 h from healthy human subjects during two 24-h measurement periods at baseline and on the fourth day of a simulated night shift protocol, in which the habitual sleep-wake cycle was delayed by 10 h. Thirty-two out of the 130 detected metabolites showed a 24-h rhythm both at baseline and during the night shift condition. Among these, 75% were driven by sleep-wake and fasting-feeding cycles rather than by the endogenous circadian clock, showing an average phase delay of 8.8 h during the night shift condition. Hence, the majority of rhythmic metabolites were misaligned relative to the endogenous circadian system during the night shift condition. This could be a key mechanism involved in the increased prevalence of adverse metabolic health effects observed in shift workers. On the individual level, the response to the night shift protocol was highly diverse, with phase shifts of rhythmic metabolite profiles ranging from a 0.2-h advance in one subject to a 12-h delay in another subject, revealing an individual metabolomic signature of circadian misalignment. Our findings provide insight into the overall and individual responses of the metabolome to circadian misalignment associated with night schedules and may thereby contribute to the development of individually tailored strategies to minimise the metabolic impacts of shift work.
Project description:Eating at a time when the internal circadian clock promotes sleep is a novel risk factor for weight gain and obesity, yet little is known about mechanisms by which circadian misalignment leads to metabolic dysregulation in humans. We studied 14 adults in a 6-d inpatient simulated shiftwork protocol and quantified changes in energy expenditure, macronutrient utilization, appetitive hormones, sleep, and circadian phase during day versus nightshift work. We found that total daily energy expenditure increased by ∼4% on the transition day to the first nightshift, which consisted of an afternoon nap and extended wakefulness, whereas total daily energy expenditure decreased by ∼3% on each of the second and third nightshift days, which consisted of daytime sleep followed by afternoon and nighttime wakefulness. Contrary to expectations, energy expenditure decreased by ∼12-16% during scheduled daytime sleep opportunities despite disturbed sleep. The thermic effect of feeding also decreased in response to a late dinner on the first nightshift. Total daily fat utilization increased on the first and second nightshift days, contrary to expectations, and carbohydrate and protein utilization were reduced on the second nightshift day. Ratings of hunger were decreased during nightshift days despite decreases in 24-h levels of the satiety hormones leptin and peptide-YY. Findings suggest that reduced total daily energy expenditure during nightshift schedules and reduced energy expenditure in response to dinner represent contributing mechanisms by which humans working and eating during the biological night, when the circadian clock is promoting sleep, may increase the risk of weight gain and obesity.
Project description:Glucose tolerance is lower in the evening and at night than in the morning. However, the relative contribution of the circadian system vs. the behavioral cycle (including the sleep/wake and fasting/feeding cycles) is unclear. Furthermore, although shift work is a diabetes risk factor, the separate impact on glucose tolerance of the behavioral cycle, circadian phase, and circadian disruption (i.e., misalignment between the central circadian pacemaker and the behavioral cycle) has not been systematically studied. Here we show--by using two 8-d laboratory protocols--in healthy adults that the circadian system and circadian misalignment have distinct influences on glucose tolerance, both separate from the behavioral cycle. First, postprandial glucose was 17% higher (i.e., lower glucose tolerance) in the biological evening (8:00 PM) than morning (8:00 AM; i.e., a circadian phase effect), independent of the behavioral cycle effect. Second, circadian misalignment itself (12-h behavioral cycle inversion) increased postprandial glucose by 6%. Third, these variations in glucose tolerance appeared to be explained, at least in part, by different mechanisms: during the biological evening by decreased pancreatic β-cell function (27% lower early-phase insulin) and during circadian misalignment presumably by decreased insulin sensitivity (elevated postprandial glucose despite 14% higher late-phase insulin) without change in early-phase insulin. We explored possible contributing factors, including changes in polysomnographic sleep and 24-h hormonal profiles. We demonstrate that the circadian system importantly contributes to the reduced glucose tolerance observed in the evening compared with the morning. Separately, circadian misalignment reduces glucose tolerance, providing a mechanism to help explain the increased diabetes risk in shift workers.
Project description:A critical barrier to successful treatment of circadian misalignment in shift workers is determining circadian phase in a clinical or field setting. Light and movement data collected passively from wrist actigraphy can generate predictions of circadian phase via mathematical models; however, these models have largely been tested in non-shift working adults. This study tested the feasibility and accuracy of actigraphy in predicting dim light melatonin onset (DLMO) in fixed night shift workers. A sample of 45 night shift workers wore wrist actigraphs before completing DLMO in the laboratory (17.0 days ± 10.3 SD). DLMO was assessed via 24 hourly saliva samples in dim light (<10 lux). Data from actigraphy were provided as input to a mathematical model to generate predictions of circadian phase. Agreement was assessed and compared to average sleep timing on non-workdays as a proxy of DLMO. Model code and an open-source prototype assessment tool are available (www.predictDLMO.com). Model predictions of DLMO showed good concordance with in-lab DLMO, with Lin's concordance coefficient of 0.70, which was twice as high as agreement using average sleep timing as a proxy of DLMO. The absolute mean error of the predictions was 2.88 h, with 76% and 91% of the predictions falling with 2 and 4 h, respectively. This study is the first to demonstrate the use of wrist actigraphy-based estimates of circadian phase as a clinically useful and valid alternative to in-lab measurement of DLMO in fixed night shift workers. Future research should explore how additional predictors may impact accuracy.
Project description:Voracious feeding, trans-continental migration and insecticide resistance make Spodoptera litura among the most difficult Asian agricultural pests to control. Larvae exhibit strong circadian behavior, feeding actively at night and hiding in soil during daytime. The daily pattern of larval metabolism was reversed, with higher transcription levels of genes for digestion (amylase, protease, lipase) and detoxification (CYP450s, GSTs, COEs) in daytime than at night. To investigate the control of these processes, we annotated nine essential clock genes and analyzed their transcription patterns, followed by functional analysis of their coupling using siRNA knockdown of interlocked negative feedback system core and repressor genes (SlituClk, SlituBmal1 and SlituCwo). Based on phase relationships and overexpression in cultured cells the controlling mechanism seems to involve direct coupling of the circadian processes to E-boxes in responding promoters. Additional manipulations involving exposure to the neonicotinoid imidacloprid suggested that insecticide application must be based on chronotoxicological considerations for optimal effectiveness.
Project description:Eight healthy human subjects were enrolled in a 6-day simulated shift work protocol. Blood samples were collected during the two 24-hour measurement periods. Blood samples were collected every 4 hours during both measurement periods. Subjects entered the lab on Day 1. At the start of Day 2, the first 24-hour measurement period was started. Subjects slept according to their habitual sleep/wake schedule, followed by a 16-hour constant posture procedure. On days 3-6, the sleep period was delayed by 10 hours. Following the third night on this schedule, subjects underwent another 24-hour measurement period. During both measurement periods, 7 blood samples were collected and PBMCs were isolated. mRNA was extracted, labelled, and hybridized to microarrays.
Project description:Background:The objective of this cross-sectional study was to evaluate the relationships between night shift work, eating habits and body mass index (BMI) among Lebanese nurses. Methods:A total of 307 nurses were randomly selected from five hospitals located in Beirut. Data about demographic and professional characteristics, anthropometric measures, dietary habits and intakes were collected through a validated questionnaire. To study the relationship between night shift work, eating habits and BMI, chi-square test, t-test and logistic regressions were used. Results:The majority of nurses (78. 2%) had irregular meals timing with a significant decrease in the number of complete meals consumed during the day and an increase in the number of snacks consumed during night (p?<?0. 05). The most consumed snacks during night shifts were sweets and potato chips. The findings highlighted that BMI and waist circumference significantly increased with the number of years of work (r?=?0.175; p?<?0.05) and the cumulative number of night shifts hours over the entire work history (r?=?0.135/p?<?0. 05). Conclusion:Night shift work is positively associated with abnormal eating patterns and BMI among Lebanese nurses. However the increase in BMI is not related to eating habits.
Project description:Birdwatching is a very popular and increasing leisure activity, and the study and observation of birds is more popular in the morning due to the greater activity among birds at that time of day. The aim of our study was to find out whether there was a relationship between the circadian preference of observers and their favourite bird species and whether it was influenced by such factors as professional status, age and gender. In an e-mail survey we asked a total of 433 Polish ornithologists (professionals) or birdwatchers (non-professionals) for their morningness-eveningness preferences (four categories) and favourite (open choice) bird species and received 143 responses. The temporal (circadian) preferences of respondents declined from early morning (35.7%) to evening/nighttime (11.4%). Circadian preference categories differed significantly by age, with early morning respondents significantly older. These preference categories did not differ significantly in terms of response time to the survey invitation or in the percentage of their favourite birds that were categorised as daytime birds. A total of 204 species were identified as favourite birds of which 34 species were mentioned by five or more respondents, with only two, the common crane Grus grus and the Eurasian pygmy owl Glaucidium passerinum mentioned by more than 10% of respondents. The white stork Ciconia ciconia was more popular with professionals than non-professionals and the swift Apus apus less popular. A significant gender × circadian preference interaction was detected for the percentage of favourite birds categorised as daytime birds, with fewer daytime birds among early morning female recorders. The presented results are obviously of a correlative nature, but open the door for further, more advanced study and suggest there may be a need to investigate temporal biases when analysing citizen-based data.