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Annual Review of Neuroscience Jul 2023This review explores the interface between circadian timekeeping and the regulation of brain function by astrocytes. Although astrocytes regulate neuronal activity... (Review)
Review
This review explores the interface between circadian timekeeping and the regulation of brain function by astrocytes. Although astrocytes regulate neuronal activity across many time domains, their cell-autonomous circadian clocks exert a particular role in controlling longer-term oscillations of brain function: the maintenance of sleep states and the circadian ordering of sleep and wakefulness. This is most evident in the central circadian pacemaker, the suprachiasmatic nucleus, where the molecular clock of astrocytes suffices to drive daily cycles of neuronal activity and behavior. In Alzheimer's disease, sleep impairments accompany cognitive decline. In mouse models of the disease, circadian disturbances accelerate astroglial activation and other brain pathologies, suggesting that daily functions in astrocytes protect neuronal homeostasis. In brain cancer, treatment in the morning has been associated with prolonged survival, and gliomas have daily rhythms in gene expression and drug sensitivity. Thus, circadian time is fast becoming critical to elucidating reciprocal astrocytic-neuronal interactions in health and disease.
Topics: Mice; Animals; Astrocytes; Circadian Rhythm; Circadian Clocks; Sleep; Suprachiasmatic Nucleus
PubMed: 36854316
DOI: 10.1146/annurev-neuro-100322-112249 -
Progress in Lipid Research Jul 2023Lipids play important roles in energy metabolism along with diverse aspects of biological membrane structure, signaling and other functions. Perturbations of lipid... (Review)
Review
Lipids play important roles in energy metabolism along with diverse aspects of biological membrane structure, signaling and other functions. Perturbations of lipid metabolism are responsible for the development of various pathologies comprising metabolic syndrome, obesity, and type 2 diabetes. Accumulating evidence suggests that circadian oscillators, operative in most cells of our body, coordinate temporal aspects of lipid homeostasis. In this review we summarize current knowledge on the circadian regulation of lipid digestion, absorption, transportation, biosynthesis, catabolism, and storage. Specifically, we focus on the molecular interactions between functional clockwork and biosynthetic pathways of major lipid classes comprising cholesterol, fatty acids, triacylglycerols, glycerophospholipids, glycosphingolipids, and sphingomyelins. A growing body of epidemiological studies associate a socially imposed circadian misalignment common in modern society with growing incidence of metabolic disorders, however the disruption of lipid metabolism rhythms in this connection has only been recently revealed. Here, we highlight recent studies that unravel the mechanistic link between intracellular molecular clocks, lipid homeostasis and development of metabolic diseases based on animal models of clock disruption and on innovative translational studies in humans. We also discuss the perspectives of manipulating circadian oscillators as a potentially powerful approach for preventing and managing metabolic disorders in human patients.
Topics: Animals; Humans; Lipid Metabolism; Circadian Rhythm; Circadian Clocks; Diabetes Mellitus, Type 2; Energy Metabolism; Metabolic Diseases; Lipids
PubMed: 37187314
DOI: 10.1016/j.plipres.2023.101235 -
Nature Communications Nov 2023Disrupted circadian rhythms have been linked to an increased risk of hypertension and cardiovascular disease. However, many studies show inconsistent findings and are...
Disrupted circadian rhythms have been linked to an increased risk of hypertension and cardiovascular disease. However, many studies show inconsistent findings and are not sufficiently powered for targeted subgroup analyses. Using the UK Biobank cohort, we evaluate the association between circadian rhythm-disrupting behaviours, blood pressure (SBP, DBP) and inflammatory markers in >350,000 adults with European white British ancestry. The independent U-shaped relationship between sleep length and SBP/DBP is most prominent with a low inflammatory status. Poor sleep quality and permanent night shift work are also positively associated with SBP/DBP. Although fully adjusting for BMI in the linear regression model attenuated effect sizes, these associations remain significant. Two-sample Mendelian Randomisation (MR) analyses support a potential causal effect of long sleep, short sleep, chronotype, daytime napping and sleep duration on SBP/DBP. Thus, in the current study, we present a positive association between circadian rhythm-disrupting behaviours and SBP/DBP regulation in males and females that is largely independent of age.
Topics: Adult; Male; Female; Humans; Blood Pressure; Shift Work Schedule; Biological Specimen Banks; Sleep; Circadian Rhythm; Sleep Initiation and Maintenance Disorders; Inflammation; United Kingdom
PubMed: 37925459
DOI: 10.1038/s41467-023-42758-6 -
Cellular and Molecular Neurobiology Aug 2023Melatonin is ubiquitous molecule with wide distribution in nature and is produced by many living organisms. In human beings, pineal gland is the major site for melatonin... (Review)
Review
Melatonin is ubiquitous molecule with wide distribution in nature and is produced by many living organisms. In human beings, pineal gland is the major site for melatonin production and to lesser extent by retina, lymphocytes, bone marrow, gastrointestinal tract, and thymus. Melatonin as a neurohormone is released into circulation wherein it penetrates all tissues of the body. Melatonin synthesis and secretion is supressed by light and enhanced by dark. Melatonin mostly exerts its effect through different pathways with melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) being the predominant type of receptor that are mainly expressed by many mammalian organs. Melatonin helps to regulate sleep patterns and circadian rhythms. In addition, melatonin acts as an antioxidant and scavenges excessive free radicals generated in the body by anti-excitatory and anti-inflammatory properties. A multiple array of other functions are displayed by melatonin that include oncostatic, hypnotic, immune regulation, reproduction, puberty timing, mood disorders, and transplantation. Deficiencies in the production or synthesis of melatonin have been found to be associated with onset of many disorders like breast cancer and neurodegenerative disorders. Melatonin could be used as potential analgesic drug in diseases associated with pain and it has quite promising role there. In the past century, a growing interest has been developed regarding the wide use of melatonin in treating various diseases like inflammatory, gastrointestinal, cancer, mood disorders, and others. Several melatonin agonists have been synthesized and are widely used in disease treatment. In this review, an effort has been made to describe the biochemistry of melatonin along with its therapeutic potential in various diseases of humans.
Topics: Animals; Humans; Melatonin; Receptors, Melatonin; Antioxidants; Circadian Rhythm; Pineal Gland; Mammals
PubMed: 36752886
DOI: 10.1007/s10571-023-01324-w -
Cell Reports Jun 2023Physiology is regulated by interconnected cell and tissue circadian clocks. Disruption of the rhythms generated by the concerted activity of these clocks is associated...
Physiology is regulated by interconnected cell and tissue circadian clocks. Disruption of the rhythms generated by the concerted activity of these clocks is associated with metabolic disease. Here we tested the interactions between clocks in two critical components of organismal metabolism, liver and skeletal muscle, by rescuing clock function either in each organ separately or in both organs simultaneously in otherwise clock-less mice. Experiments showed that individual clocks are partially sufficient for tissue glucose metabolism, yet the connections between both tissue clocks coupled to daily feeding rhythms support systemic glucose tolerance. This synergy relies in part on local transcriptional control of the glucose machinery, feeding-responsive signals such as insulin, and metabolic cycles that connect the muscle and liver. We posit that spatiotemporal mechanisms of muscle and liver play an essential role in the maintenance of systemic glucose homeostasis and that disrupting this diurnal coordination can contribute to metabolic disease.
Topics: Mice; Animals; Circadian Clocks; Circadian Rhythm; Liver; Muscle, Skeletal; Glucose
PubMed: 37267101
DOI: 10.1016/j.celrep.2023.112588 -
Frontiers in Endocrinology 2023
Topics: Endocrinology; Circadian Rhythm
PubMed: 37600720
DOI: 10.3389/fendo.2023.1263823 -
JAMA Network Open Jan 2024Observational studies have associated anorexia nervosa with circadian rhythms and sleep traits. However, the direction of causality and the extent of confounding by...
IMPORTANCE
Observational studies have associated anorexia nervosa with circadian rhythms and sleep traits. However, the direction of causality and the extent of confounding by psychosocial comorbidities in these associations are unknown.
OBJECTIVES
To investigate the association between anorexia nervosa and circadian and sleep traits through mendelian randomization and to test the associations between a polygenic risk score (PRS) for anorexia nervosa and sleep disorders in a clinical biobank.
DESIGN, SETTING, AND PARTICIPANTS
This genetic association study used bidirectional 2-sample mendelian randomization with summary-level genetic associations between anorexia nervosa (from the Psychiatric Genomics Consortium) and chronotype and sleep traits (primarily from the UK Biobank). The inverse-variance weighted method, in addition to other sensitivity approaches, was used. From the clinical Mass General Brigham (MGB) Biobank (n = 47 082), a PRS for anorexia nervosa was calculated for each patient and associations were tested with prevalent sleep disorders derived from electronic health records. Patients were of European ancestry. All analyses were performed between February and August 2023.
EXPOSURES
Genetic instruments for anorexia nervosa, chronotype, daytime napping, daytime sleepiness, insomnia, and sleep duration.
MAIN OUTCOMES AND MEASURES
Chronotype, sleep traits, risk of anorexia nervosa, and sleep disorders derived from a clinical biobank.
RESULTS
The anorexia nervosa genome-wide association study included 16 992 cases (87.7%-97.4% female) and 55 525 controls (49.6%-63.4% female). Genetic liability for anorexia nervosa was associated with a more morning chronotype (β = 0.039; 95% CI, 0.006-0.072), and conversely, genetic liability for morning chronotype was associated with increased risk of anorexia nervosa (β = 0.178; 95% CI, 0.042-0.315). Associations were robust in sensitivity and secondary analyses. Genetic liability for insomnia was associated with increased risk of anorexia nervosa (β = 0.369; 95% CI, 0.073-0.666); however, sensitivity analyses indicated bias due to horizontal pleiotropy. The MGB Biobank analysis included 47 082 participants with a mean (SD) age of 60.4 (17.0) years and 25 318 (53.8%) were female. A PRS for anorexia nervosa was associated with organic or persistent insomnia in the MGB Biobank (odds ratio, 1.10; 95% CI, 1.03-1.17). No associations were evident for anorexia nervosa with other sleep traits.
CONCLUSIONS AND RELEVANCE
The results of this study suggest that in contrast to other metabo-psychiatric diseases, anorexia nervosa is a morningness eating disorder and further corroborate findings implicating insomnia in anorexia nervosa. Future studies in diverse populations and with subtypes of anorexia nervosa are warranted.
Topics: Female; Humans; Male; Middle Aged; Anorexia Nervosa; Circadian Rhythm; Genetic Risk Score; Genome-Wide Association Study; Sleep; Sleep Initiation and Maintenance Disorders; Adult; Aged
PubMed: 38175645
DOI: 10.1001/jamanetworkopen.2023.50358 -
Nature Communications Dec 2023Daily eating/fasting cycles synchronise circadian peripheral clocks, involved in the regulation of the cardiovascular system. However, the associations of daily meal and...
Daily eating/fasting cycles synchronise circadian peripheral clocks, involved in the regulation of the cardiovascular system. However, the associations of daily meal and fasting timing with cardiovascular disease (CVD) incidence remain unclear. We used data from 103,389 adults in the NutriNet-Santé study. Meal timing and number of eating occasions were estimated from repeated 24 h dietary records. We built multivariable Cox proportional-hazards models to examine their association with the risk of CVD, coronary heart disease and cerebrovascular disease. In this study, having a later first meal (later than 9AM compared to earlier than 8AM) and last meal of the day (later than 9PM compared to earlier than 8PM) was associated with a higher risk of cardiovascular outcomes, especially among women. Our results suggest a potential benefit of adopting earlier eating timing patterns, and coupling a longer nighttime fasting period with an early last meal, rather than breakfast skipping, in CVD prevention.
Topics: Adult; Humans; Female; Prospective Studies; Cardiovascular Diseases; Diet; Circadian Rhythm; Fasting; Feeding Behavior
PubMed: 38097547
DOI: 10.1038/s41467-023-43444-3 -
Frontiers in Endocrinology 2024
Topics: Humans; Circadian Rhythm; Circadian Clocks; Obesity
PubMed: 38577573
DOI: 10.3389/fendo.2024.1387889 -
Osteoarthritis and Cartilage Nov 2023Osteoarthritis (OA) is the most common age-related joint disease, affecting articular cartilage and other joint structures, causing severe pain and disability. Due to a... (Review)
Review
Osteoarthritis (OA) is the most common age-related joint disease, affecting articular cartilage and other joint structures, causing severe pain and disability. Due to a limited understanding of the underlying disease pathogenesis, there are currently no disease-modifying drugs for OA. Circadian rhythms are generated by cell-intrinsic timekeeping mechanisms which are known to dampen during ageing, increasing disease risks. In this review, we focus on one emerging area of chondrocyte biology, the circadian clocks. We first provide a historical perspective of circadian clock discoveries and the molecular underpinnings. We will then focus on the expression and functions of circadian clocks in articular cartilage, including their rhythmic target genes and pathways, links to ageing, tissue degeneration, and OA, as well as tissue niche-specific entrainment pathways. Further research into cartilage clocks and ageing may have broader implications in the understanding of OA pathogenesis, the standardization of biomarker detection, and the development of novel therapeutic routes for the prevention and management of OA and other musculoskeletal diseases.
Topics: Humans; Osteoarthritis; Cartilage, Articular; Chondrocytes; Circadian Clocks; Circadian Rhythm
PubMed: 37230460
DOI: 10.1016/j.joca.2023.05.010