Metabolic Rhythms Research Articles

Circadian rhythm and the influence of light on parameters related to calcium metabolism in stroke patients admitted for rehabilitation

Hospitalized stroke patients are at high risk of developing circadian disruption due to lack of natural sunlight. This may affect the circadian rhythm of the calcium metabolism. This study is a secondary explorative analysis from a Randomized Controlled Trial. Acute stroke patients requiring a minimum of two weeks of rehabilitation were randomized to an Intervention unit (IU) equipped with naturalistic light or a Control unit (CU) with standard indoor lighting. Blood was drawn across 24 h at inclusion and discharge in 45 patients, 25 from the IU and 20 from the CU. Calcium showed significant rhythmicity at inclusion and discharge in both groups. Alkaline phosphatase, parathyroid hormone (PTH), and Vitamin D exhibited no significant rhythmicity at inclusion or discharge in either group while phosphate exhibited rhythmicity at discharge in the CU. PTH levels were elevated in the CU group compared to the IU group at time of discharge. Of the measured parameters, only calcium exhibited circadian rhythmicity after stroke. Naturalistic light did not have any influence on the rhythmicity, indicating that light may not be the main circadian regulator of the circadian oscillations that regulate calcium metabolism. PTH seems to be decreased by naturalistic light.

Physiological rhythms and metabolic regulation: Shining light on skeletal muscle.

Metabolic regulation is essential for maintaining homeostasis in response to fluctuating dietary nutrient availability. In this review, we explore how metabolic health can be affected by the temporal alignment between daily behavioural patterns (e.g., eating, physical activity and sleep) and recurring cycles in underlying physiology (e.g., 'circadian' rhythms). Misalignment within and/or between these patterns and cycles can lead to metabolic dysregulation, increasing the risk of chronic disease states such as obesity, type 2 diabetes and cardiovascular disease. Conversely, metabolic health can be improved by strategically aligning certain behavioural patterns with endogenous rhythms in physiology. Dietary interventions based upon this reasoning are referred to as chrono-nutrition strategies. Skeletal muscle is an important tissue in relation to both whole-body metabolism and behaviour and plays a central role in how physiological rhythms respond to the timing of nutrient delivery/availability. Few studies have examined rhythms in metabolism within human skeletal muscle, providing opportunities to advance current understanding of how nutrient timing affects muscle metabolism.

Chronic restraint stress affects the diurnal rhythms of gut microbial composition and metabolism in a mouse model of depression

BackgroundDepression is a common mental disorder accompanied by gut microbiota dysbiosis, which disturbs the metabolism of the host. While diurnal oscillation of the intestinal microbiota is involved in regulating host metabolism, the characteristics of the intestinal microbial circadian rhythm in depression remain unknown. Our aim was to investigate the microbial circadian oscillation signature and related metabolic pathways in a mouse model with depression-like behaviours.MethodsChronic restraint stress (CRS) was used to induce depressive-like behaviours in C57BL/6J mice. The open field test (OFT) and forced swimming test (FST) were used to evaluate anxiety- and depressive-like behaviours in the control and CRS groups. Afterwards, faecal samples from the two groups were collected every four hours from ZT2 (9:00 am) to ZT22 (5:00 am). Faecal 16 S rRNA gene sequencing and metabolomics analysis were performed, and the microbial circadian rhythm was analysed via the MetaCycle package in R/RStudio.ResultsCRS mice exhibited depressive-like behaviours after 4 weeks of restriction. Alpha- and beta-diversity analyses revealed that the microbial composition in control and CRS mice oscillated throughout the day. The circadian rhythm analyses revealed that at the phylum level, Bacteroidota, Firmicutes, Cyanobacteria and Patescibacteria showed circadian rhythmicity in the CRS group. At the genus level, Dubosiella and Romboutsia showed circadian rhythmicity in the control group, and Dubosiella abundance was correlated with tryptophan and galactose metabolism. In the CRS group, Bacteroides, Parabacteroides, and Rikenellaceae_RC9_gut_group showed circadian rhythmicity; among these genera, Parabacteroides was related to tryptophan metabolism, axon regeneration, phenylalanine metabolism and tyrosine metabolism.ConclusionOur data highlight the importance of observing the diurnal oscillation of the microbiome in host with depressive-like states. Rhythmicity in the microbiome may affect the host by regulating distinct metabolic pathways during the light and dark phases. A better combination of microbiota composition and oscillation would help to offer novel insight into key genera and their potential effects on depression.

The main sources of molecular organization in the cell. Atlas of self-organized and self-regulated dynamic biostructures.

One of the most important goals of contemporary biology is to understand the principles of the molecular order underlying the complex dynamic architecture of cells. Here, we present an overview of the main driving forces involved in the cellular molecular complexity and in the emergent functional dynamic structures, spanning from the most basic molecular organization levels to the complex emergent integrative systemic behaviors. First, we address the molecular information processing which is essential in many complex fundamental mechanisms such as the epigenetic memory, alternative splicing, regulation of transcriptional system, and the adequate self-regulatory adaptation to the extracellular environment. Next, we approach the biochemical self-organization, which is central to understand the emergency of metabolic rhythms, circadian oscillations, and spatial traveling waves. Such a complex behavior is also fundamental to understand the temporal compartmentalization of the cellular metabolism and the dynamic regulation of many physiological activities. Numerous examples of biochemical self-organization are considered here, which show that practically all the main physiological processes in the cell exhibit this type of dynamic molecular organization. Finally, we focus on the biochemical self-assembly which, at a primary level of organization, is a basic but important mechanism for the order in the cell allowing biomolecules in a disorganized state to form complex aggregates necessary for a plethora of essential structures and physiological functions. In total, more than 500 references have been compiled in this review. Due to these main sources of order, systemic functional structures emerge in the cell, driving the metabolic functionality towards the biological complexity.

Circadian rhythm disruption, Shift work and its Metabolic impact

Shift work has an irreplaceable role in many companies and posts, however the negative health impacts are ineluctable, so it is worthy to clarify the possible influence that can post on the metabolism and therefore causing dangerous disorders. The relationship between the shift work and circadian rhythm including the master clock (SCN) and peripheral clock in the tissue and the external environment is researched, in the meantime the various effects are also mentioned. The main focus was on the metabolism, contending that glucose and lipid metabolism has affected by the changes of the circadian rhythm and potential consequences like diabetes and obesity might emerge. Additionally, insulin sensitivity drops as the circadian phases shifts, with accompanied by the risk of type 2 diabetes. Other effects like influences on the hormone secretion and functioning does also shows relationships with metabolic rhythms, for instance the melatonin reduction can leads several diseases. With the clear understanding of these relationships further clinical studies show be able to utilize the mechanisms and produce therapeutic interventions

Circadian Proteomics Reassesses the Temporal Regulation of Metabolic Rhythms by Chlamydomonas Clock.

Circadian clocks execute temporal regulation of metabolism by modulating the timely expression of genes. Clock regulation of mRNA synthesis was envisioned as the primary driver of these daily rhythms. mRNA oscillations often do not concur with the downstream protein oscillations, revealing the importance to study protein oscillations. Chlamydomonas reinhardtii is a well-studied miniature plant model. We quantitatively probed the Chlamydomonas proteome for two subsequent circadian cycles using high throughput SWATH-DIA mass spectrometry. We quantified > 1000 proteins, half of which demonstrate circadian rhythms. Among these rhythmic proteins, > 90% peak around subjective midday or midnight. We uncovered key enzymes involved in Box C/D pathway, amino acid biosynthesis, fatty acid (FA) biosynthesis and peroxisomal β-oxidation of FAs are driven by the clock, which were undocumented from earlier transcriptomic studies. Proteins associated with key biological processes such as photosynthesis, redox, carbon fixation, glycolysis and TCA cycle show extreme temporal regulation. We conclude that circadian proteomics is required to complement transcriptomic studies to understand the complex clock regulation of organismal biology. We believe our study will not only refine and enrich the evaluation of temporal metabolic processes in C. reinhardtii but also provide a novel understanding of clock regulation across species.

Time-restricted feeding reduces cardiovascular disease risk in obese mice.

Disrupted feeding and fasting cycles as well as chronic high fat diet (HFD)-induced obesity are associated with cardiovascular disease risk factors. We designed studies that determined whether two weeks of time-restricted feeding (TRF) intervention in mice fed a chronic HFD would reduce cardiovascular disease risk factors. Mice were fed a normal diet (ND; 10% fat) ad libitum or HFD (45% fat) for 18 weeks ad libitum to establish diet-induced obesity. ND or HFD mice were continued on ad libitum diet or subjected to TRF (limiting food availability to 12 hr only during the dark phase) during the final two weeks of the feeding protocol. TRF improved whole-body metabolic diurnal rhythms without a change in body weight. HFD mice showed reduced blood pressure dipping compared to ND, which was restored by TRF. Further, TRF reduced aortic wall thickness, decreased aortic stiffness, as well as increased kidney tubular brush border integrity, decreased renal medullary fibrosis, and reduced renal medullary T cell inflammation in HFD mice. These findings indicate that TRF may be an effective intervention for improving vascular and kidney health in a model of established diet-induced obesity.

Identifying Candidate Genes Related to Soybean (Glycine max) Seed Coat Color via RNA-Seq and Coexpression Network Analysis.

The quality of soybeans is reflected in the seed coat color, which indicates soybean quality and commercial value. Researchers have identified genes related to seed coat color in various plants. However, research on the regulation of genes related to seed coat color in soybeans is rare. In this study, four lines of seed coats with different colors (medium yellow 14, black, green, and brown) were selected from the F2:5 population, with Beinong 108 as the female parent and green bean as the male parent, and the dynamic changes in the anthocyanins in the seed coat were stained with 4-dimethylaminocinnamaldehyde (DMACA) during the grain maturation process (20 days from grain drum to seed harvest). Through RNA-seq of soybean lines with four different colored seed coats at 30 and 50 days after seeding, we can further understand the key pathways and gene regulation modules between soybean seed coats of different colors. DMACA revealed that black seed coat soybeans produce anthocyanins first and have the deepest staining. Clustering and principal component analysis (PCA) of the RNA-seq data divided the eight samples into two groups, resulting in 16,456 DEGs, including 5359 TFs. GO and KEGG enrichment analyses revealed that the flavonoid biosynthesis, starch and sucrose metabolism, carotenoid biosynthesis, and circadian rhythm pathways were significantly enriched. We also conducted statistical and expression pattern analyses on the differentially expressed transcription factors. Based on weighted gene coexpression network analysis (WGCNA), we identified seven specific modules that were significantly related to the four soybean lines with different seed coat colors. The connectivity and functional annotation of genes within the modules were calculated, and 21 candidate genes related to soybean seed coat color were identified, including six transcription factor (TF) genes and three flavonoid pathway genes. These findings provide a theoretical basis for an in-depth understanding of the molecular mechanisms underlying differences in soybean seed coat color and provide new genetic resources.

Chronic sleep deprivation disturbs energy balance modulated by suprachiasmatic nucleus efferents in mice

BackgroundEpidemiologic researches show that short sleep duration may affect feeding behaviors resulting in higher energy intake and increased risk of obesity, but the further mechanisms that can interpret the causality remain unclear. The circadian rhythm is fine-tuned by the suprachiasmatic nucleus (SCN) as the master clock, which is essential for driving rhythms in food intake and energy metabolism through neuronal projections to the arcuate nucleus (ARC) and paraventricular nucleus (PVN).ResultsWe showed that chronic SD-induced aberrant expressions of AgRP/NPY and POMC attributed to compromised JAK/STAT3 signals and reduced energy expenditure in the mice, which can be rescued with AAV-genetic overexpression of BMAL1 into SCN. The potential mechanism may be related to the disruptions of SCN efferent mediated by BMAL1.ConclusionsChronic SD impairs energy balance through directly dampening BMAL1 expression, probably in the transcription level, in the SCN, which in turn affects the neuron projections to ARC and PVN. Remarkably, we provide evidence that may explain the causal mechanisms associated with sleep curtailment and obesity in adolescents.Graphical

Time-Restricted Feeding Reinforces Gut Rhythmicity by Restoring Rhythms in Intestinal Metabolism in a Jetlag Mouse Model.

Circadian disturbances result in adverse health effects, including gastrointestinal symptoms. We investigated which physiological pathways in jejunal mucosa were disrupted during chronic jetlag and prevented during time-restricted feeding (TRF). Enteroids from Bmal1+/+ and Bmal1-/- mice were used to replicate the processes that were affected by chronic jetlag and rescued by TRF. C57BL/6J male mice were subjected to chronic jetlag or night-TRF for 4 weeks. An around-the-clock bulk-RNA sequencing study was performed on the jejunal mucosa. Bmal1+/+ and Bmal1-/- mouse enteroids were generated to study the jejunal epithelial clock dependency of rhythmic jejunal processes. Chronic jetlag disrupted the rhythmicity of jejunal clock genes and the jejunal transcriptome, which was partially rescued by TRF. Genes whose rhythm was altered by chronic jetlag but prevented by TRF were primarily associated with nutrient transport, lipid metabolism, ketogenesis, and cellular organization. Invivo, chronic jetlag caused a phase shift in the rhythmic accumulation of neutral lipids and induced a diurnal rhythm in the number of crypt epithelial cells, both of which were prevented by TRF. Invitro, enteroids replicated the invivo rhythmic accumulation of neutral lipids in a clock-dependent manner, whereas the rhythm of S phase proliferation was ultradian in both genotypes of enteroids. This pioneering transcriptomic study demonstrates that TRF acts as a robust entrainer during chronic jetlag, realigning disturbances in the circadian clock and the transcriptome involved in metabolic functions in the jejunal mucosa. Enteroids can replicate the rhythmic accumulation of neutral lipids dependent on the jejunal epithelial clock, enabling these functions to be studied invitro.

Differences in cerebral spontaneous neural activity correlate with gene-specific transcriptional signatures in primary angle-closure glaucoma.

This study was aimed to investigate frequency-specific LFO changes and their correlation with gene pathways in PACG using transcriptome-neuroimaging analysis. Resting-state fMRI (Rs-fMRI) data were acquired from individuals with PACG and healthy controls for evaluating the amplitude of low-frequency oscillations (ALFF) across different frequency bands such as the full band, slow-4 band, and slow-5 band. Transcriptome analysis integrated information from the Allen Human Brain Atlas (AHBA) through gene set enrichment analysis, protein-protein interaction network construction, and specific expression analysis, aiming to clarify the link between ALFF patterns and gene expression profiles in PACG. Statistical analyses, including one-sample t-tests and two-sample t-tests, were used to assess ALFF differences between groups, while partial least squares (PLS) regression was applied to explore the associations between ALFF and transcriptome data. This study identifies significant variations in ALFF values in PACG patients, observed consistently across multiple frequency bands, including slow-4 and slow-5. Enrichment analysis indicates that these genes are primarily involved in cellular components such as the cytosol and cytoplasm, molecular functions like protein binding, and key pathways, including metabolic and circadian rhythms, epithelial signaling in Helicobacter pylori infection, and glutathione metabolism. Protein-protein interaction (PPI) analysis further underscores the role of PACG-related genes in forming a functional network, highlighting hub genes critical for various biological processes. This study establishes a connection between the molecular mechanisms of PACG and alterations in brain function and gene expression, providing valuable perspectives on the fundamental processes impacting low-frequency oscillations in PACG.

Tau pathology induced alteration in neuronal activity disrupt sleep and cerebral metabolic rhythms in the P301S PS19 mouse model of tauopathy

AbstractBackgroundAlzheimer’s disease is defined by the pathological aggregation of amyloid‐beta and hyperphosphorylated tau. AD patients often exhibit other symptoms like metabolic and sleep dysfunction. Currently, it is unclear if impairments are a cause or consequence of Aβ or tau aggregation. Previously, we demonstrated cerebral and peripheral changes in glucose elevate brain lactate levels stimulating wake. Further, previous work showed tau pathology corresponds with decreased sleep. Currently, it’s unclear what mechanisms drive sleep changes or if it relates to metabolic dysfunction. Therefore, we investigated how tau pathology impacts sleep and metabolism in P301S mice.MethodsTo examine peripheral metabolism, glucose tolerance tests were conducted on P301S and wild‐type mice(female). Recordings of indirect calorimetry over 3 days further explored peripheral metabolism. Paired glucose and lactate biosensors in the hippocampi tracked sub‐second fluctuations of brain interstitial fluid (ISF) to observe cerebral metabolic changes. EEG and EMG recorded cortical activity over a 3‐day period and spectral analysis investigated sleep/wake architecture.ResultTau aggregation preserves peripheral glucose tolerance and diurnal rhythms of brain glucose/lactate, normally lost in aged controls, suggesting increased glucose utilization. Similarly, P301S mice show increased respiratory exchange ratio suggesting heightened carbohydrate utilization. Conversely, they exhibit diminished energy expenditure. EEG spectral analysis revealed increased delta, increased theta, and decreased beta with pathology, suggesting disrupted GABA activity and sleep drive. Starting early in pathology, mice display increased wake and decreased NREM/REM. Effects on total sleep depend heavily on decreased REM bout number and duration.ConclusionBlood glucose levels in P301S mice fail to rise in response to glucose injection. Brain glucose/lactate fluctuations are maintained suggesting tau pathology preserves glucose utilization. Conversely, decreased NREM and REM and increased wake were exhibited with tau pathology. EEG spectral analysis indicates decreased beta activity, suggesting diminished GABA activity. Increased theta during NREM suggests increased pressure to transition to REM sleep. Reduced sleep drive is illustrated by increased delta in wake. Together, tau pathology reduces sleep drive and ability to switch between vigilant states despite increased sleep need. These results suggest that tau pathology causes excitatory/inhibitory imbalance and sleep impairment but does not contribute to profound effects on cerebral metabolic rhythms.

Effects of Time-Restricted Eating on Body Composition, Biomarkers of Metabolism, Inflammation, Circadian System and Oxidative Stress in Overweight and Obesity: An Exploratory Review.

Obesity is a chronic, complex and multi-factorial condition with an increasing prevalence worldwide. Irregular eating schedules might be a contributing factor to these numbers through the dysregulation of the circadian system. Time-restricted eating (TRE), an approach that limits eating windows, has been studied as a strategy to treat obesity, aligning eating occasions with metabolic circadian rhythms. This review aims to provide an overview of the impact of TRE protocols on metabolic, inflammatory, oxidative stress, and circadian rhythm biomarkers in people with overweight or obesity. Most studies report significant weight loss following TRE protocols. While glucose levels decreased in nearly all TRE interventions, only a few studies demonstrated statistically significant differences when compared to the control groups. The findings for CRP and TNF-α were inconsistent, with limited significant differences. Changes in lipid profile changes were variable and generally did not reach statistical significance. Both 4-hour and 6-hour TRE interventions significantly reduced 8-isoprostane levels. Additionally, TRE significantly altered clock gene expression, as well as that of genes associated with metabolic regulation in subcutaneous adipose tissue. While the evidence is still inconsistent, limiting eating to a consistent daily window of 8 to 12 hours can improve insulin sensitivity, reduce blood glucose, cholesterol and triglyceride levels and promote weight loss. These effects are likely attributable to both direct metabolic impacts and indirect benefits from weight loss and improved dietary habits. However, data on circadian, inflammatory, and specific metabolic biomarkers remain scarce and occasionally contradictory, highlighting the need for further research on these interventions.

Exploring sugar allocation and metabolic shifts in cassava plants infected with Cassava common mosaic virus (CsCMV) under long-day photoperiod: diel changes in source and sink leaves.

Cassava common mosaic virus (CsCMV) is a potexvirus that impairs chloroplast and metabolism, causing significant yield losses to cassava crops. Crop yield depends on diel rhythms, influencing carbon allocation and growth, and sugar signaling also impacting light-dark rhythms. This study aimed to elucidate the early impact of CsCMV infection on diel carbon allocation, metabolism, and defense mechanisms in both source and sink cassava leaves before storage root bulking. Soluble sugar and starch concentrations were examined over a 24-h cycle (16:8 photoperiod) in CsCMV-infected plants. The expression of an array of genes-carbohydrate metabolism, SnRK1 activity marker, defense, circadian marker-was analyzed at ZT6, ZT16 and ZT24/ZT0. In CsCMV-infected source leaves, at ZT6, sucrose increased whereas glucose, fructose and sucrose rose at night. An increase in Suc:hexose ratio and upregulation of SnRK1 activity marker genes and PR1 transcripts were found in infected leaves, suggesting a combination of altered carbon metabolism and defense response mechanisms against the viral infection. GIGANTEA, a clock-controlled gene, showed a reduced expression in infected leaves at ZT6 and ZT24/ZT0, suggesting a circadian phase shift compared with uninfected control plants. Additionally, starch mobilization transcripts were downregulated at ZT24/ZT0, though starch content remained unchanged during the 24-h cycle. In sink leaves, a transient peak of maltose (ZT6) was observed. Our findings suggest that CsCMV disrupts the plant's natural rhythms of sugar metabolism and allocation. Spikes in sucrose levels may serve as infection signals in the internal daily clock of the plant, influencing plant responses during the cassava-CsCMV interaction.

Circadian Alterations in Brain Metabolism Linked to Cognitive Deficits During Hepatic Ischemia-Reperfusion Injury Using [1H-13C]-NMR Metabolomics.

Background: Hepatic ischemia-reperfusion injury (HIRI) is known to affect cognitive functions, with particular concern for its impact on brain metabolic dynamics. Circadian rhythms, as a crucial mechanism for internal time regulation within organisms, significantly influence metabolic processes in the brain. This study aims to explore how HIRI affects hippocampal metabolism and its circadian rhythm differences in mice, and to analyze how these changes are associated with cognitive impairments. Methods: A C57BL/6 male mouse model was used, simulating HIRI through hepatic ischemia-reperfusion surgery, with a sham operation conducted for the control group. Cognitive functions were evaluated using open field tests, Y-maze tests, and novel object recognition tests. Magnetic resonance spectroscopic imaging (MRSI) technology, combined with intravenous injection of [2-13C]-acetate and [1-13C]-glucose, was utilized to analyze metabolic changes in the hippocampus of HIRI mice at different circadian time points (Zeitgeber Time ZT0, 8:00 and ZT12, 20:00). Circadian rhythms regulate behavioral, physiological, and metabolic rhythms through transcriptional feedback loops, with ZT0 at dawn (lights on) and ZT12 at dusk (lights off). Results: HIRI mice exhibited significant cognitive impairments in behavioral tests, particularly in spatial memory and learning abilities. MRSI analysis revealed significant circadian rhythm differences in the concentration of metabolites in the hippocampus, with the enrichment concentrations of lactate, alanine, glutamate, and taurine showing different trends at ZT0 compared to ZT12, highlighting the important influence of circadian rhythms on metabolic dysregulation induced by HIRI. Conclusions: This study highlights the significant impact of HIRI on brain metabolic dynamics in mice, especially in the hippocampal area, and for the first time reveals the differences in these effects within circadian rhythms. These findings not only emphasize the association between HIRI-induced cognitive impairments and changes in brain metabolism but also point out the crucial role of circadian rhythms in this process, offering new metabolic targets and timing considerations for therapeutic strategies against HIRI-related cognitive disorders.

Meta-analysis of experimental studies of the effect of melatonin monotherapy on the levels of thyroid hormones and glucocorticoids in rats kept under standard condition

Melatonin is known to modulate circadian and seasonal rhythms in metabolism, reproduction, and behavior. However, the effect of exogenous melatonin supplementation on the functioning of the thyroid and adrenal glands in species without a clear seasonality in reproduction is still unclear. Using a meta-analysis of publications, to investigate the effect of melatonin monotherapy on the concentrations of pituitary thyroid-stimulating hormone, thyroid hormones (TG), pituitary adrenocorticotropic hormone and corticosterone (CS) in rats kept under standard laboratory conditions. In our work, using the Review Manager 5.3 program, we conducted a meta-analysis of publications examining the effect of melatonin monotherapy on the functioning of the thyroid gland (22 papers) and adrenal glands (20 papers) in rats kept under standard conditions. According to the results of our meta-analysis, the effects of melatonin on the levels of TG and CS depend on the dose and duration of therapy. A decrease in TG and CS was associated with therapy lasting no more than 4-5 weeks and with high doses of melatonin. An increase in CS and a trend toward increased TG levels were observed with longer therapy. However, a few studies have observed a decrease in TG with very long-term melatonin therapy (≥32 weeks). Among all TGs, total thyroxine (T4) showed maximum sensitivity to exogenous melatonin, which indicates the influence of melatonin on the secretory function of the thyroid gland. In addition, melatonin increased the relative weight of the adrenal glands. There was no convincing evidence that the effects of melatonin were influenced by the route and timing of administration, or the timing of blood sampling. As a result, exogenous melatonin can modulate TG and CS levels, even in species without a clear seasonality in reproductive function.

Transcriptome-Based Revelation of the Effects of Sleep Deprivation on Hepatic Metabolic Rhythms in Tibetan Sheep (Ovis aries).

Sleep deprivation (SD) disrupts circadian rhythms; however, its effects on SD and the mechanisms involved require further investigation. Previous studies on SD were mainly conducted on rodents, such as mice, with few studies on its effects on the liver of large diurnal animals, such as sheep. In this study, we used a Tibetan sheep model for the first time to investigate the effects of SD on the liver by exposing Tibetan sheep (Ovis aries) to 7 days of SD (6 h/day) and performed transcriptome sequencing analysis on liver samples taken at 4 h intervals over 24 h. The results revealed that SD significantly altered the circadian expression of genes and their expression patterns in the liver of Tibetan sheep. Enrichment analysis of the circadian rhythm-altered genes revealed changes in the pathways related to lipid metabolism in the liver. Further evidence from serum markers and gene expression analyses using qualitative real-time polymerase chain reaction and Oil Red O and apoptosis staining indicated that SD leads to abnormal lipid metabolism in the liver, potentially causing liver damage. Therefore, our results suggest that SD disrupts the circadian rhythms of metabolism-related genes in the Tibetan sheep liver, thereby affecting metabolic homeostasis.

Association of estimated glucose disposal rate with incident cardiovascular disease under different metabolic and circadian rhythm states: findings from a national population-based prospective cohort study

BackgroundRecent studies have shown that both metabolic syndrome and circadian rhythm syndrome are firmly associated with the occurrence of cardiovascular disease (CVD), with insulin resistance playing a significant role. The estimated glucose disposal rate (eGDR) is considered to be a reliable surrogate marker for insulin resistance. However, the relationship between eGDR and CVD under different metabolic and circadian rhythm states has not been thoroughly studied, and large-scale prospective cohort studies are needed to clarify this relationship.MethodsThis study is based on the China Health and Retirement Longitudinal Study (CHARLS), recruiting individuals aged 45 and above with complete eGDR data. The eGDR was calculated by the formula: eGDR(mg/kg/min) = 21.158 − (0.09 × WC) − (3.407 × hypertension) − (0.551 × HbA1c) [WC (cm), hypertension (yes = 1/no = 0), and HbA1c (%)] (Zabala et al. in Cardiovasc Diabetol 20(1):202; 2021).Participants were divided into four subgroups based on the quartiles (Q) of eGDR.The cumulative incidence rates and hazard ratios (HR) with 95% confidence intervals (CI) were calculated, with the lowest eGDR quartile (representing the highest degree of insulin resistance) as the reference. Participants were further divided into subgroups based on the diagnosis of Metabolic syndrome (MetS) or circadian syndrome (CircS) to explore the relationship between eGDR and CVD under different metabolic and circadian rhythm conditions. The dose–response relationship between eGDR and CVD incidence was investigated using a restricted cubic spline (RCS) based on a Cox regression model. Receiver operating characteristic (ROC) curves were generated to assess the predictive value of eGDR for CVD incidence. A clinical decision curve analysis (DCA) was also conducted to assess the clinical utility of the basic model.Results6507 participants were included, with a median age of 58 years [52 years, 64 years], and 55% were female. Over a median follow-up duration of 87 months, 679 first-episode CVD events were recorded, including heart disease and stroke. The RCS curves demonstrated a significant dose–response relationship between eGDR and the incidence of first-presentation CVD in different metabolic and circadian rhythm subgroups (all P-values < 0.001, non-linearity P > 0.05). eGDR exhibited a significant linear relationship with all outcomes (non-linearity P < 0.05). The Kaplan–Meier cumulative incidence curves showed that as eGDR levels increased, the cumulative incidence rates of first CVD, heart disease, and stroke gradually decreased from Q1 to Q4 groups. Significant differences were observed across all metabolic and circadian rhythm subgroups (log-rank test P < 0.001). Through the Cox proportional hazards model, we confirmed a significant association between baseline eGDR levels and first-onset CVD, heart disease, and stroke. Subgroup analyses indicated that the predictive ability of eGDR for CVD risk varied across different Body mass index (BMI) (P for interaction = 0.025) and age (P for interaction = 0.045) subgroups. Mediation analysis revealed that CircS partially mediated this association. Furthermore, time-dependent ROC curves demonstrated the potential of eGDR as a predictor of CVD risk, revealing possible differences in the model's application across different cardiovascular conditions.ConclusioneGDR is an independent predictor of CVD risk, with lower eGDR levels being closely associated with a higher risk of CVD (including heart disease and stroke). In populations with MetS or CircS, the association between lower eGDR levels and increased risk is more pronounced.

Night shift-induced circadian disruption: links to initiation of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and risk of hepatic cancer.

The circadian system plays a crucial role in regulating metabolic homeostasis at both systemic and tissue levels by synchronizing the central and peripheral clocks with exogenous time cues, known as zeitgebers (such as the light/dark cycle). Our body's behavioral rhythms, including sleep-wake cycles and feeding-fasting patterns, align with these extrinsic time cues. The body cannot effectively rest and repair itself when circadian rhythms are frequently disrupted. In many shift workers, the internal rhythms fail to fully synchronize with the end and start times of their shifts. Additionally, exposure to artificial light at night (LAN), irregular eating patterns, and sleep deprivation contribute to circadian disruption and misalignment. Shift work and jet lag disrupt the normal circadian rhythm of liver activity, resulting in a condition known as "circadian disruption". This disturbance adversely affects the metabolism and homeostasis of the liver, contributing to excessive fat accumulation and abnormal liver function. Additionally, extended working hours, such as prolonged night shifts, may worsen the progression of non-alcoholic fatty liver disease (NAFLD) toward non-alcoholic steatohepatitis (NASH) and increase disease severity. Studies have demonstrated a positive correlation between night shift work (NSW) and elevated liver enzymes, indicative of hepatic metabolic dysfunction, potentially increasing the risk of hepatocellular carcinoma (HCC) related to NAFLD. This review consolidates research findings on circadian disruption caused by NSW, late chronotype, jet lag, and social jet lag, drawing insights from studies involving both humans and animal models that investigate the effects of these factors on circadian rhythms in liver metabolism.

Eating Around the Clock: Circadian Rhythms of Eating and Metabolism.

The time of day that we eat is increasingly recognized as contributing as importantly to overall health as the amount or quality of the food we eat. The endogenous circadian clock has evolved to promote intake at optimal times when an organism is intended to be awake and active, but electric lights and abundant food allow eating around the clock with deleterious health outcomes. In this review, we highlight literature pertaining to the effects of food timing on health, beginning with animal models and then translation into human experiments. We emphasize the pitfalls and opportunities that technological advances bring in bettering understanding of eating behaviors and their association with health and disease. There is great promise for restricting the timing of food intake both in clinical interventions and in public health campaigns for improving health via nonpharmacological therapies.