AIM: Exposure to light at night and meal time misaligned with the light/dark (LD) cycle-typical features of daily life in modern 24/7 society-are associated with negative effects on health. To understand the mechanism, we developed a novel protocol of complex chronodisruption (CD) in which we exposed female rats to four weekly cycles consisting of 5-day intervals of constant light and 2-day intervals of food access restricted to the light phase of the 12:12 LD cycle. METHODS: We examined the effects of CD on behavior, estrous cycle, sleep patterns, glucose homeostasis and profiles of clock- and metabolism-related gene expression (using RT qPCR) and liver metabolome and lipidome (using untargeted metabolomic and lipidomic profiling). RESULTS: CD attenuated the rhythmic output of the central clock in the suprachiasmatic nucleus via Prok2 signaling, thereby disrupting locomotor activity, the estrous cycle, sleep patterns, and mutual phase relationship between the central and peripheral clocks. In the periphery, CD abolished Per1,2 expression rhythms in peripheral tissues (liver, pancreas, colon) and worsened glucose homeostasis. In the liver, it impaired the expression of NAD+, lipid, and cholesterol metabolism genes and abolished most of the high-amplitude rhythms of lipids and polar metabolites. Interestingly, CD abolished the circadian rhythm of Cpt1a expression and increased the levels of long-chain acylcarnitines (ACar 18:2, ACar 16:0), indicating enhanced fatty acid oxidation in mitochondria. CONCLUSION: Our data show the widespread effects of CD on metabolism and point to ACars as biomarkers for CD due to misaligned sleep and feeding patterns.

• Keywords
• acylcarnitine, chronodisruption, clock, female, glucose homeostasis, liver, metabolome, pancreas, rat, sleep, suprachiasmatic nucleus,
• MeSH
• Circadian Clocks * physiology   MeSH
• Circadian Rhythm * physiology   MeSH
• Photoperiod MeSH
• Liver * metabolism   MeSH
• Carnitine * analogs & derivatives   metabolism   MeSH
• Rats MeSH
• Metabolome * physiology   MeSH
• Rats, Sprague-Dawley MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• acylcarnitine MeSH Browser
• Carnitine * MeSH

The topic of human circadian rhythms is not only attracting the attention of clinical researchers from various fields but also sparking a growing public interest. The circadian system comprises the central clock, located in the suprachiasmatic nucleus of the hypothalamus, and the peripheral clocks in various tissues that are interconnected; together they coordinate many daily activities, including sleep and wakefulness, physical activity, food intake, glucose sensitivity and cardiovascular functions. Disruption of circadian regulation seems to be associated with metabolic disorders (particularly impaired glucose tolerance) and cardiovascular disease. Previous clinical trials revealed that disturbance of the circadian system, specifically due to shift work, is associated with an increased risk of type 2 diabetes mellitus. This review is intended to provide clinicians who wish to implement knowledge of circadian disruption in diagnosis and strategies to avoid cardio-metabolic disease with a general overview of this topic.

• Keywords
• cardiovascular disease risk, circadian clock, circadian rhythm disruption, glucose tolerance, insulin sensitivity, time restricted eating, type 2 diabetes mellitus,
• MeSH
• Chronobiology Disorders physiopathology   complications   MeSH
• Circadian Rhythm * physiology   MeSH
• Diabetes Mellitus, Type 2 physiopathology   metabolism   MeSH
• Cardiovascular Diseases * etiology   physiopathology   MeSH
• Humans MeSH
• Metabolic Diseases * physiopathology   metabolism   etiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The lifestyle of human society is drifting apart from the natural environmental cycles that have influenced it since its inception. These cycles were fundamental in structuring the daily lives of people in the pre-industrial era, whether they were seasonal or daily. Factors that disrupt the regularity of human behaviour and its alignment with solar cycles, such as late night activities accompanied with food intake, greatly disturb the internal temporal organization in the body. This is believed to contribute to the rise of the so-called diseases of civilization. In this review, we discuss the connection between misalignment in daily (circadian) regulation and its impact on health, with a focus on cardiovascular and metabolic disorders. Our aim is to review selected relevant research findings from laboratory and human studies to assess the extent of evidence for causality between circadian clock disruption and pathology. Keywords: Circadian clock, Chronodisruption, Metabolism, Cardiovascular disorders, Spontaneously hypertensive rat, Human, Social jetlag, Chronotype.

• MeSH
• Chronobiology Disorders physiopathology   metabolism   complications   MeSH
• Circadian Clocks physiology   MeSH
• Circadian Rhythm * physiology   MeSH
• Cardiovascular Diseases * metabolism   etiology   epidemiology   physiopathology   MeSH
• Humans MeSH
• Metabolic Diseases * metabolism   epidemiology   physiopathology   etiology   MeSH
• Disease Models, Animal MeSH
• Risk Factors MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

STUDY OBJECTIVES: Social jetlag manifests as a difference in sleep timing on workdays and free days. Social jetlag is often associated with shorter, lower-quality sleep, so it is unclear how much the chronic circadian misalignment contributes to observed negative health outcomes. We aimed to (1) investigate associations between social jetlag, chronotype (one of its determinants), and the levels of health markers, (2) describe factors associated with social jetlag, and (3) examine whether working from home can reduce social jetlag. METHODS: Adult respondents participated in a nationally representative longitudinal survey of Czech households (individuals in each wave: n2018/19/20 = 5132/1957/1533), which included Munich ChronoType Questionnaire to evaluate chronotype and social jetlag. A subset provided blood samples (n2019 = 1957) for detection of nine biomarkers and was surveyed in three successive years (social jetlag calculated for n2018/19/20 = 3930/1601/1237). Data were analyzed by nonparametric univariate tests and mixed effects multivariate regression with social jetlag, chronotype, sex, age, body-mass index, and reported diseases as predictors and biomarker levels as outcomes. RESULTS: Higher social jetlag (≥0.65 h) was significantly associated with increased levels of total cholesterol and low-density lipoprotein cholesterol, particularly in participants older than 50 years (Mann-Whitney, men: pCHL = 0.0005, pLDL = 0.0009; women: pCHL = 0.0079, pLDL = 0.0068). Extreme chronotypes were associated with cardiovascular disease risk markers regardless of social jetlag (Kruskal-Wallis, p < 0.0001). Commuting to work and time stress were identified as important contributors to social jetlag. Individual longitudinal data showed that working from home decreased social jetlag and prolonged sleep. CONCLUSIONS: We report significant associations between sleep phase preference, social jetlag, and cardio-metabolic biomarkers.

• Keywords
• Biomarkers, Cholesterol, Chronotype, Circadian Rhythm, Humans, Lipoproteins, HDL, Lipoproteins, LDL, Models, Statistical, Social jetlag,
• MeSH
• Biomarkers MeSH
• Cholesterol MeSH
• Circadian Rhythm * MeSH
• Adult MeSH
• Jet Lag Syndrome MeSH
• Humans MeSH
• Metabolic Diseases * complications   MeSH
• Surveys and Questionnaires MeSH
• Sleep MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers MeSH
• Cholesterol MeSH

Previous research has shown that sleep deprivation, low quality sleep or inconvenient sleeping times are associated with lower quality of life. However, research of the longitudinal effects of sleep on quality of life is scarce. Hence, we know very little about the long-term effect of changes in sleep duration, sleep quality and the time when individuals sleep on quality of life. Using longitudinal data from three waves of the Czech Household Panel Study (2018-2020) containing responses from up to 4,523 respondents in up to 2,155 households, the study examines the effect of changes in sleep duration, sleep quality and social jetlag on satisfaction with life, happiness, work stress, subjective health and wellbeing. Although sleep duration and timing are important, panel analyses reveal that sleep quality is the strongest predictor of all sleep variables in explaining both within-person and between-person differences in quality of life indicators.

• MeSH
• Jet Lag Syndrome MeSH
• Sleep Quality MeSH
• Quality of Life * MeSH
• Humans MeSH
• Surveys and Questionnaires MeSH
• Sleep * physiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: The MTNR1B gene encodes a receptor for melatonin, a hormone regulating biorhythms. Disruptions in biorhythms contribute to the development of type 2 diabetes mellitus (T2DM). Genetic studies suggest that variability in the MTNR1B gene affects T2DM development. Our aim was to compare the distribution of the genetic variant rs10830963 between persons differing in glucose tolerance in a sample of the Czech population (N=1206). We also evaluated possible associations of the polymorphism with insulin sensitivity, beta cell function, with the shape of glucose, insulin and C-peptide trajectories measured 7 times during a 3-hour oral glucose tolerance test (OGTT) and with glucagon response. In a subgroup of 268 volunteers we also evaluated sleep patterns and biorhythm. RESULTS: 13 persons were diagnosed with T2DM, 119 had impaired fasting blood glucose (IFG) and/or impaired glucose tolerance (IGT). 1074 participants showed normal results and formed a control group. A higher frequency of minor allele G was found in the IFG/IGT group in comparison with controls. The GG constellation was present in 23% of diabetics, in 17% of IFG/IGT probands and in 11% of controls. Compared to CC and CG genotypes, GG homozygotes showed higher stimulated glycemia levels during the OGTT. Homozygous as well as heterozygous carriers of the G allele showed lower very early phase of insulin and C-peptide secretion with unchanged insulin sensitivity. These differences remained significant after excluding diabetics and the IFG/IGT group from the analysis. No associations of the genotype with the shape of OGTT-based trajectories, with glucagon or with chronobiological patterns were observed. However, the shape of the trajectories differed significantly between men and women. CONCLUSION: In a representative sample of the Czech population, the G allele of the rs10830963 polymorphism is associated with impaired early phase of beta cell function, and this is evident even in healthy individuals.

• Keywords
• MTNR1B gene, OGTT trajectories, beta cell function, glucose tolerance, insulin sensitivity, rs10830963, type 2 daibetes mellitus,
• MeSH
• C-Peptide MeSH
• Diabetes Mellitus, Type 2 * epidemiology   genetics   MeSH
• Glucagon MeSH
• Glucose MeSH
• Insulin MeSH
• Insulin Resistance * genetics   MeSH
• Kinetics MeSH
• Blood Glucose MeSH
• Humans MeSH
• Glucose Intolerance * epidemiology   genetics   MeSH
• Prediabetic State * MeSH
• Receptor, Melatonin, MT2 * genetics   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• C-Peptide MeSH
• Glucagon MeSH
• Glucose MeSH
• Insulin MeSH
• Blood Glucose MeSH
• MTNR1B protein, human MeSH Browser
• Receptor, Melatonin, MT2 * MeSH