Search Results (19)

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the management of type 2 diabetes and obesity, yet their actions extend beyond glycemic control and weight loss. This narrative review synthesizes current preclinical and clinical evidence examining the bidirectional relationship between glucagon-like peptide-1 (GLP-1) receptor agonists and circadian biology. A structured literature search was conducted in PubMed using combinations of the terms ‘GLP-1,’ ‘circadian,’ ‘chronobiology,’ ‘sleep,’ ‘obesity,’ and ‘type 2 diabetes’ through January 2026. Accumulating evidence indicates that GLP-1 physiology is closely coupled to circadian timing systems and sleep–wake regulation. In this narrative review, we synthesize emerging data that reframe GLP-1RAs as chronometabolic modulators, acting at the intersection of metabolism, circadian biology, and sleep. We review circadian control of GLP-1 secretion by intestinal L-cells, emphasizing the role of core clock genes and the vulnerability of incretin rhythms to circadian misalignment from shift work, nocturnal light exposure, and sleep loss. We then examine GLP-1 receptor signaling within central and peripheral clock networks, including feedback effects on hypothalamic and hepatic circadian regulation. Emerging data suggest that GLP-1 signaling is under circadian regulation and may, in turn, influence central and peripheral clock systems. Comparative discussion of semaglutide, liraglutide, and tirzepatide highlights agent-specific pharmacokinetics and emerging clinical data linking GLP-1RA therapy to sleep outcomes, particularly obstructive sleep apnea. Finally, we outline translational opportunities for chronotherapy and precision medicine, positioning GLP-1RAs as integrative tools for metabolic and sleep-related disease rather than purely weight-centric therapies. We propose that GLP-1 receptor agonists may function as chronometabolic modulators, with potential implications for personalized chronopharmacological strategies in metabolic disease. Full article

Burnout is increasingly recognized as both a psychosocial and a chronobiological disorder characterized by endocrine dysregulation and circadian disruption. It arises from chronic occupational stress and manifests through psychological, physical, and physiological symptoms. Although psychosocial determinants are well established, the biological and chronobiological mechanisms, particularly those involving cortisol and melatonin, remain less explored. This systematic review synthesizes current evidence on hormonal and circadian dysregulation in burnout and complements it with exploratory observational data from healthcare professionals. Peer-reviewed studies evaluating endocrine or circadian biomarkers in individuals with burnout were systematically reviewed. In addition, an exploratory observational analysis was carried out among 195 Romanian clinicians using an adapted Maslach Burnout Inventory. Morning salivary cortisol was measured once at 9 a.m. in a small subsample (n = 26) to provide preliminary physiological data. Because only a single time point was obtained, these values were interpreted as indicative of stress-related activation rather than circadian rhythm. Thirty-seven studies met the inclusion criteria. Across the literature, burnout was associated with altered HPA-axis activity, blunted diurnal cortisol variation, and irregular melatonin secretion related to shift work and disrupted sleep–wake cycles. Complementary exploratory data from our Romanian cohort indicated strong correlations between burnout severity, physical symptoms, and higher morning cortisol values among shift-working clinicians. These findings are preliminary and not representative of full circadian profiles. Burnout should be considered both a psychosocial and a systemic disorder influenced by endocrine and circadian dysregulation. Recognizing alterations in cortisol and melatonin as objective indicators may facilitate earlier detection and inform chronobiological interventions such as optimized scheduling, light exposure management, or melatonin therapy. The observational data presented here is preliminary and intended to generate hypotheses; future research should employ repeated cortisol sampling under controlled Zeitgeber conditions to confirm circadian associations. Full article

Background. Although melatonin is widely used in Sleep Medicine for its chronobiological action, its potent antioxidant and mitochondrial regulatory effects, as well as its immunomodulatory and anti-inflammatory functions, make it of interest as a cytoprotective agent in several chronic pathologies. These actions are evident at doses higher than those used for sleep disorders. Even at high doses, melatonin’s adverse effects are few, mild, and self-limited or resolve quickly after discontinuation of treatment. Based on its safety profile, we treated melatonin for sleep disorders in the presence of comorbidities with doses ≥ 40 mg daily. Methods. This was a retrospective mixed observational analytical design comprising a retrospective uncontrolled cohort analysis and a cross-sectional study. Eighty-one patients (57 female) with sleep disorders ranging in age from 55 to 98 years (mean 74.4 years) were treated with melatonin 40 to 200 mg daily (mean 72.7 mg) were examined. Fifty-six percent of patients received treatment for more than 4 years. The control group for the cross-sectional analysis included 81 patients over 52 years of age, matched by age and sex and not receiving melatonin but having sleep disorders within the same period. Results. A significant decrease was observed in arterial hypertension, ischemic heart disease and diabetes mellitus after melatonin administration. Analysis of clinical laboratory variables indicated no changes in the treated group versus the untreated group, except for a lower alkaline phosphatase concentration in patients who received melatonin. Conclusions. These findings suggest a beneficial effect of cytoprotective doses of melatonin on the cardiovascular and metabolic profile in an aged population. Full article

The root conformation of soybean is critical to achieve physiological activities such as nodulation and nitrogen fixation; however, the molecular determinants behind genotypic differences in its early development remain poorly described. In this study, we compared the characteristics of the soybean varieties HN75 and HN76 and examined developmental disparities in their root architectural characteristics and the transcriptomic profiles of radicles between them. The plant height and 100-grain weight of HN75, which had a longer growth cycle of 170 days, were slightly higher than those of HN76, which had a shorter growth cycle of 120 days. However, the numbers of pods and grains per plant were slightly lower. In terms of quality traits, HN75 had a higher oil content (23.40% versus 21.50%), whereas HN76 had a higher protein content (41.39% versus 35.71%). HN75 exhibited markedly superior root elongation (13.27 cm versus 10.15 cm), enhanced lateral root proliferation, and significantly greater nodule formation (19.53 versus 8.60 nodules per plant) relative to HN76 at 30 days post-germination, notwithstanding comparable nodule biomass. Chronobiological analysis (0–96 h post-germination) identified a pivotal developmental window of 48–72 h post-germination. Transcriptomic profiling of radicle tissues revealed 4792 differentially expressed genes (DEGs) in HN75 compared to 896 in HN76 during this critical interval, indicating substantially heightened transcriptional activity in HN75. Functional annotation enrichment demonstrated that HN75 DEGs were significantly enriched in phytohormone signalling cascades and isoprenoid biosynthetic pathways, whereas HN76 DEGs were predominantly associated with protein processing within the endoplasmic reticulum. We screened for eight genes (Glyma 10G071400, Glyma 13G057500, Glyma 08G016900, Glyma 09G028000, Glyma 18G265800, Glyma 03G032800, Glyma 02G064100, and Glyma 01G238600) that may play a role in the critical period of radicle development by performing network analyses and verified their dramatic changes in expression during this period by qRT-PCR. These results elucidate varietal-specific physiological and molecular mechanisms governing early radicle development in soybeans. These findings unravel mechanisms governing leguminous radicle development while establishing molecular blueprints for engineering cultivation protocols that would enhance soybean sustainability in edaphically constrained environments. Full article

Animal behavior diversity is a key element of biodiversity, and the establishment of an ethogram provides a crucial framework for exploring the relationship between behavioral patterns and environmental factors. However, the development of ethograms and the quantitative analysis of behavioral diversity in fish remain underexplored. In this study, focal animal sampling and instantaneous scan sampling methods, paired with the PAE (Posture-Act-Environment) coding system, were employed to investigate the ethogram and reproductive behavior diversity of silver carp. The findings revealed 12 postures, 20 actions, and 34 behaviors documented during the breeding period of silver carp. Analysis of reproductive behavior diversity revealed that the absolute behavioral diversity index (H), relative behavioral diversity index (r), and regulated diversity index (r-variable) all peaked during the 10–15 h interval following induced spawning. Notably, significant differences (p < 0.001) were observed in these indices across different post-induction time intervals and between sexes. Throughout the breeding cycle, females demonstrated lower diversity and intensity in reproductive behaviors compared to males, suggesting distinct reproductive strategies between the sexes. The reproductive behavior of silver carp exhibited distinct chronobiological disorganization patterns. This study provides a scientific basis for future research on the behavioral ecology of silver carp and the conservation of their wild populations. Full article

The recently observed circadian oscillations of the intestinal microbiota underscore the profound nature of the human–microbiome relationship and its importance for health. Together with the discovery of circadian clocks in non-photosynthetic gut bacteria and circadian rhythms in anucleated cells, these findings have indicated the possibility that virtually all microorganisms may possess functional biological clocks. However, they have also raised many essential questions concerning the fundamentals of biological timekeeping, its evolution, and its origin. This narrative review provides a comprehensive overview of the recent literature in molecular chronobiology, aiming to bring together the latest evidence on the structure and mechanisms driving microbial biological clocks while pointing to potential applications of this knowledge in medicine. Moreover, it discusses the latest hypotheses regarding the evolution of timing mechanisms and describes the functions of peroxiredoxins in cells and their contribution to the cellular clockwork. The diversity of biological clocks among various human-associated microorganisms and the role of transcriptional and post-translational timekeeping mechanisms are also addressed. Finally, recent evidence on metabolic oscillators and host–microbiome communication is presented. Full article

Background: Men are more likely than women to have subthreshold overeating disorders. Lifestyle plays a role as a determinant, while chronotype is an emerging factor. Chronotype explains the natural preferences of wakefulness and activity throughout the day: evening chronotypes (E-Types), those most productive in the evening, have been linked with unhealthy dietary patterns and a higher propensity to substance addiction than morning types (M-Types). Methods: We carried out a cross-sectional study on 750 overweight or obese adults (70% females, 48 ± 10 years, BMI 31.7 ± 5.8 kg/m²). The Binge-Eating Scale, the Yale Food Addiction Scale 2.0 (YFAS 2.0), the reduced Morningness-Eveningness Questionnaire (rMEQ), and the MEDAS questionnaire were used to assess binge eating, food addiction, chronotype, and adherence to the Mediterranean diet, respectively. Results: No differences in BES binge-eating and FA food-addiction scores occurred between chronotypes, but we found significant interactions between sex × rMEQ score. While women showed the same prevalence for binge eating and food addiction across all chronotypes, binge eating and food addiction risk increased with reducing rMEQ score in men, indicating that being male and E-Type increases the risk association of binge eating and/or food addiction prevalence. Conclusions: chronotype is associated with binge eating and food addiction in men, emphasizing the link between chronobiology and sex differences as determinants in appetite and eating behaviour dysregulation and in overweight and obesity. Full article

Objective: There is evidence that reduced sleep duration increases hunger, appetite, and food intake, leading to metabolic diseases, such as type 2 diabetes and obesity. However, the impact of sleep timing, irrespective of its duration and on the regulation of hunger and appetite, is less clear. We aimed to evaluate the impact of sleep loss during the late vs. early part of the night on the regulation of hunger, appetite, and desire for food. Methods: Fifteen normal-weight ([mean ± SEM] body-mass index: 23.3 ± 0.4 kg/m²) healthy men were studied in a randomized, balanced, crossover design, including two conditions of sleep loss, i.e., 4 h sleep during the first night-half (‘late-night sleep loss’), 4 h sleep during the second night-half (‘early-night sleep loss’), and a control condition with 8h sleep (‘regular sleep’), respectively. Feelings of hunger and appetite were assessed through visual analogue scales, and plasma ghrelin and leptin were measured from blood samples taken before, during, and after night-time sleep. Results: Ghrelin and feelings of hunger and appetite, as well as the desire for food, were increased after ‘late-night sleep loss’, but not ‘early-night sleep loss’, whereas leptin remained unaffected by the timing of sleep loss. Conclusions: Our data indicate that timing of sleep restriction modulates the effects of acute sleep loss on ghrelin and appetite regulation in healthy men. ‘Late-night sleep loss’ might be a risk factor for metabolic diseases, such as obesity and type 2 diabetes. Thereby, our findings highlight the metabolic relevance of chronobiological sleep timing. Full article

Cavefish are vertebrates living in extreme subterranean environments with no light, temperature changes, and limited food. Circadian rhythms in these fish are suppressed in natural habitats. However, they can be found in artificial light–dark cycles and other zeitgebers. The molecular circadian clock has its peculiarities in cavefish. In Astyanax mexicanus, the core clock mechanism is tonically repressed in the caves due to the overactivation of the light input pathway. A lack of functional light input pathway but rather the entrainment of circadian genes’ expression by scheduled feeding were revealed in more ancient Phreatichthys andruzzii. Different evolutionarily determined irregularities in the functioning of molecular circadian oscillators can be expected in other cavefish. The unique property of some species is the existence of surface and cave forms. Along with the ease of maintenance and breeding, it made cavefish a promising model for chronobiological studies. At the same time, a divergence of the circadian system between cavefish populations requires the strain of origin to be indicated in further research. Full article

This study analysed circadian variation changes in blood pressure (BP), the pain pressure threshold (PPT) and the elasticity of tissue in patients with fibromyalgia (FM) after a whole-body photobiomodulation (PBM) treatment. This was a tripled-blinded randomized clinical trial including forty participants with FM. Participants using validated self-measurement BP devices attained readings that were used to calculate the circadian variation. Additionally, a standard pressure algometer of 1cm2 was used to assess 13 tender points by exerting a pressure of up to 4 kg, and strain elastography assessed the elasticity of tissue. Circadian variations in BP showed significant differences after the PBM intervention (p = 0.036). When comparing PPT between groups, statistically significant differences were found in the occiput (p = 0.039), low cervical (p = 0.035), trapezius (p = 0.037), second rib (p < 0.001) and medial epicondyle points (p = 0.006). Furthermore, there were statistically significant differences in both the trapezius and the forearm at the distal dorsal third SEL values (p ≤ 0.001) when comparing groups. Whole-body PBM produces changes in circadian blood pressure, the pain pressure threshold and the elasticity of tissue after a treatment program was carried out. However, more studies are needed to corroborate our findings as well as to better understand the underlying mechanisms. Full article

The aim of this study was to analyze the impact of circadian variation of blood pressure (BP) in patients with chronic musculoskeletal pain (CPM). A further purpose was to study differences in circadian variation of BP between genders and the correlation between BP circadian variation and pain. We performed a cross-sectional, observational study in which seventy-five participants with CMP participated. Circadian variation in BP was calculated using the diurnal/nocturnal BP ratio, and all participants used validated self-measurement BP devices. The Numeric Pain Rating Scale was used to assess pain perception. All circadian BP values from participants who suffered from CPM followed pathologic cardiovascular parameters (BP ratio < 10%). When comparing BP ratios between genders, statistically significant differences were found (p = 0.011). BP itself did not correlate with pain in any subgroup. Circadian variations of BP in those suffering from CMP are shown and new possibilities of research and treatment are proposed. Full article

The conception of novel anticancer delivery systems and the combination of chronobiology with nanotechnology may provide a powerful tool to optimize cancer therapy. In this work, polyethylenimine (PEI) has been used to complex p53 encoded plasmid DNA (pDNA), and the anticancer drug methotrexate (MTX) has also been loaded into the vectors. To investigate the influence of circadian clock on drug/gene delivery efficiency, HeLa, C33A and fibroblast cells have been transfected with developed PEI/pDNA/MTX delivery vectors at six different time points. Phenomena as the cellular uptake/internalization, drug/gene delivery and p53 protein production have been evaluated. The cell-associated MTX fluorescence have been monitored, and p53 protein levels quantified. In HeLa and C33A cancer cells, significant levels of MTX were found for T8 and T12. For these time points, a high amount of p53 protein was quantified. Confocal microscopy images showed successful HeLa cell’s uptake of PEI/pDNA/MTX particles, at T8. In comparison, poor levels of MTX and p53 protein were found in fibroblasts; nevertheless, results indicated rhythmicity. Data demonstrate the influence of circadian rhythm on both cancer-cells targeting ability and transfection performance of PEI/pDNA/MTX carriers and seemed to provide the optimum time for drug/gene delivery. This report adds a great contribution to the field of cancer chronobiology, highlighting the relationship between circadian rhythm and nanodelivery systems, and charting the path for further research on a, yet, poorly explored but promising topic. Full article

South American camelids are definitive hosts of Fasciola hepatica. However, their capacity to participate in the transmission and epidemiology of fascioliasis has never been appropriately studied. Therefore, an F. hepatica isolate from Argentine llama is for the first time analyzed using Galba truncatula lymnaeids from Bolivia. Experimental follow-up studies included egg embryogenesis, miracidial infection of lymnaeid snails, intramolluscan larval development, cercarial production, chronobiology of cercarial shedding, vector survival to infection, and metacercarial infectivity of mammal host. Shorter prepatent and patent periods were leading to markedly lower cercarial production, shorter cercarial shedding, and a higher negative impact on snail survival. The usually low liver fluke prevalences and intensities and low daily fecal outputs indicate that llamas do not substantially contribute to fascioliasis transmission. The defecating behavior in dung piles far from freshwater collections prevents lymnaeid infection by eggs shed by this camelid. All results suggest the reservoir role of the llama to be negligible and, therefore, no priority within control measures in endemic areas. However, llamas may play a disease-spreading role if used as pack animals in rural areas. In the Northern Bolivian Altiplano human hyperendemic area, neither llamas nor alpacas should be considered for control measures within a One Health action. Full article

Imaging technologies are being deployed on cabled observatory networks worldwide. They allow for the monitoring of the biological activity of deep-sea organisms on temporal scales that were never attained before. In this paper, we customized Convolutional Neural Network image processing to track behavioral activities in an iconic conservation deep-sea species—the bubblegum coral Paragorgia arborea—in response to ambient oceanographic conditions at the Lofoten-Vesterålen observatory. Images and concomitant oceanographic data were taken hourly from February to June 2018. We considered coral activity in terms of bloated, semi-bloated and non-bloated surfaces, as proxy for polyp filtering, retraction and transient activity, respectively. A test accuracy of 90.47% was obtained. Chronobiology-oriented statistics and advanced Artificial Neural Network (ANN) multivariate regression modeling proved that a daily coral filtering rhythm occurs within one major dusk phase, being independent from tides. Polyp activity, in particular extrusion, increased from March to June, and was able to cope with an increase in chlorophyll concentration, indicating the existence of seasonality. Our study shows that it is possible to establish a model for the development of automated pipelines that are able to extract biological information from times series of images. These are helpful to obtain multidisciplinary information from cabled observatory infrastructures. Full article

Tailoring medical interventions to a particular patient and pathology has been termed personalized medicine. The outcome of cancer treatments is improved when the intervention is timed in accordance with the patient’s internal time. Yet, one challenge of personalized medicine is how to consider the biological time of the patient. Prerequisite for this so-called chronotherapy is an accurate characterization of the internal circadian time of the patient. As an alternative to time-consuming measurements in a sleep-laboratory, recent studies in chronobiology predict circadian time by applying machine learning approaches and mathematical modelling to easier accessible observables such as gene expression. Embedding these results into the mathematical dynamics between clock and cancer in mammals, we review the precision of predictions and the potential usage with respect to cancer treatment and discuss whether the patient’s internal time and circadian observables, may provide an additional indication for individualized treatment timing. Besides the health improvement, timing treatment may imply financial advantages, by ameliorating side effects of treatments, thus reducing costs. Summarizing the advances of recent years, this review brings together the current clinical standard for measuring biological time, the general assessment of circadian rhythmicity, the usage of rhythmic variables to predict biological time and models of circadian rhythmicity. Full article