Bmal1 integrates circadian function and temperature sensing in the suprachiasmatic nucleus.

Circadian regulation and temperature dependency are important orchestrators of molecular pathways. How the integration between these two drivers is achieved, is not understood. We monitored circadian- and temperature-dependent effects on transcription dynamics of cold-response protein RNA Binding Motif 3 (Rbm3). Temperature changes in the mammalian master circadian pacemaker, the suprachiasmatic nucleus (SCN), induced Rbm3 transcription and regulated its circadian periodicity, whereas the core clock gene Per2 was unaffected. Rbm3 induction depended on a full Brain And Muscle ARNT-Like Protein 1 (Bmal1) complement: reduced Bmal1 erased Rbm3 responses and weakened SCN circuit resilience to temperature changes. By focusing on circadian and temperature dependency, we highlight weakened transmission between core clock and downstream pathways as a potential route for reduced circadian resilience.

Chronic phase advances reduces recognition memory and increases vascular cognitive dementia-like impairments in aged mice.

Disrupted or atypical light-dark cycles disrupts synchronization of endogenous circadian clocks to the external environment; extensive circadian rhythm desynchrony promotes adverse health outcomes. Previous studies suggest that disrupted circadian rhythms promote neuroinflammation and neuronal damage post-ischemia in otherwise healthy mice, however, few studies to date have evaluated these health risks with aging. Because most strokes occur in aged individuals, we sought to identify whether, in addition to being a risk factor for poor ischemic outcome, circadian rhythm disruption can increase risk for vascular cognitive impairment and dementia (VCID). We hypothesized that repeated 6 h phase advances (chronic jet lag; CJL) for 8 weeks alters cerebrovascular architecture leading to increased cognitive impairments in aged mice. Female CJL mice displayed impaired spatial processing during a spontaneous alternation task and reduced acquisition during auditory-cued associative learning. Male CJL mice displayed impaired retention of the auditory-cued associative learning task 24 h following acquisition. CJL increased vascular tortuosity in the isocortex, associated with increased risk for vascular disease. These results demonstrate that CJL increased sex-specific cognitive impairments coinciding with structural changes to vasculature in the brain. We highlight that CJL may accelerate aged-related functional decline and could be a crucial target against disease progression.

Circadian disturbances by altering the light-dark cycle negatively affects hematopoietic function of bone marrow in mice.

Circadian rhythms in metabolically active tissues are crucial for maintaining physical health. Circadian disturbance (CD) can cause various health issues, such as metabolic abnormalities and immune and cognitive dysfunctions. However, studies on the role of CD in immune cell development and differentiation, as well as the rhythmic expression of the core clock genes and their altered expression under CD, remain unclear. Therefore, we exposed C57bl/6j mice to repeated reversed light-dark cycles for 90 days to research the effects of CD on bone marrow (BM) hematopoietic function. We also researched the effects of CD on endogenous circadian rhythms, temporally dependent expression in peripheral blood and myeloid leukocytes, environmental homeostasis within BM, and circadian oscillations of hematopoietic-extrinsic cues. Our results confirmed that when the light and dark cycles around mice were frequently reversed, the circadian rhythmic expression of the two main circadian rhythm markers, the hypothalamic clock gene, and serum melatonin, was disturbed, indicating that the body was in a state of endogenous CD. Furthermore, CD altered the temporally dependent expression of peripheral blood and BM leukocytes and destroyed environmental homeostasis within the BM as well as circadian oscillations of hematopoietic-extrinsic cues, which may negatively affect BM hematopoiesis in mice. Collectively, these results demonstrate that circadian rhythms are vital for maintaining health and suggest that the association between CD and hematopoietic dysfunction warrants further investigation.

Analysis of Phase Separation of EARLY FLOWERING 3.

Phase separation is an important mechanism for regulating various cellular functions. The EARLY FLOWERING 3 (ELF3) protein, an essential element of the EVENING COMPLEX (EC) involved in circadian clock regulation, has been shown to undergo phase separation. ELF3 is known to significantly influence elongation growth and flowering time regulation, and this is postulated to be due to whether the protein is in the dilute or phase-separated state. Here, we present a brief overview of methods for analyzing ELF3 phase separation in vitro, including the generation of phase diagrams as a function of pH and salt versus protein concentrations, optical microscopy, fluorescence recovery after photobleaching (FRAP), and turbidity assays.

Dynamic encoding of temperature in the central circadian circuit coordinates physiological activities.

The circadian clock regulates animal physiological activities. How temperature reorganizes circadian-dependent physiological activities remains elusive. Here, using in-vivo two-photon imaging with the temperature control device, we investigated the response of the Drosophila central circadian circuit to temperature variation and identified that DN1as serves as the most sensitive temperature-sensing neurons. The circadian clock gate DN1a's diurnal temperature response. Trans-synaptic tracing, connectome analysis, and functional imaging data reveal that DN1as bidirectionally targets two circadian neuronal subsets: activity-related E cells and sleep-promoting DN3s. Specifically, behavioral data demonstrate that the DN1a-E cell circuit modulates the evening locomotion peak in response to cold temperature, while the DN1a-DN3 circuit controls the warm temperature-induced nocturnal sleep reduction. Our findings systematically and comprehensively illustrate how the central circadian circuit dynamically integrates temperature and light signals to effectively coordinate wakefulness and sleep at different times of the day, shedding light on the conserved neural mechanisms underlying temperature-regulated circadian physiology in animals.

Moral decision-making at night and the impact of night work with blue-enriched white light or warm white light: a counterbalanced crossover study.

BACKGROUND: Cognitive function, including moral decision-making abilities, can be impaired by sleep loss. Blue-enriched light interventions have been shown to ameliorate cognitive impairment during night work. This study investigated whether the quality of moral decision-making during simulated night work differed for night work in blue-enriched white light, compared to warm white light. METHODS: Using a counterbalanced crossover design, three consecutive night shifts were performed in blue-enriched white light (7000 K) and warm white light (2500 K) provided by ceiling-mounted LED luminaires (photopic illuminance: ∼200 lx). At 03:30 h on the second shift (i.e. twice) and at daytime (rested), the Defining Issues Test-2, assessing the activation of cognitive schemas depicting different levels of cognitive moral development, was administered. Data from 30 (10 males, average age 23.3 ± 2.9 years) participants were analysed using linear mixed-effects models. RESULTS: Activation of the post-conventional schema (P-score), that is, the most mature moral level, was significantly lower for night work in warm white light (EMM; estimated marginal mean = 44.3, 95% CI = 38.9-49.6; pholm=.007), but not blue-enriched white light (EMM = 47.5, 95% CI = 42.2-52.8), compared to daytime (EMM = 51.2, 95% CI = 45.9-56.5). Also, the P-score was reduced for night work overall (EMM = 45.9, 95% CI = 41.1-50.8; p=.008), that is, irrespective of light condition, compared to daytime. Neither activation of the maintaining norms schema (MN-score), that is, moderately developed moral level, nor activation of the personal interest schema (i.e. the lowest moral level) differed significantly between light conditions. The MN-score was however increased for night work overall (EMM = 26.8, 95% CI = 23.1-30.5; p=.033) compared to daytime (EMM = 23.1, 95% CI = 18.9-27.2). CONCLUSION: The results indicate that moral decisions during simulated night work in warm white light, but not blue-enriched white light, become less mature and principle-oriented, and more rule-based compared to daytime, hence blue-enriched white light may function as a moderator. Further studies are needed, and the findings should be tentatively considered.Trial registration: ClinicalTrials.gov (ID: NCT03203538) Registered: 26/06/2017; https://clinicaltrials.gov/study/NCT03203538.

The quality of moral decision-making, seen as the activation of cognitive schemas depicting different levels of moral development, was reduced during simulated night work in warm white light, but not blue-enriched light, compared to daytime.The quality of moral decision-making sems to be reduced during simulated night work, compared to daytime.More studies assessing the impact of night work and light interventions on the quality of moral decision-making are needed to validate these tentative findings.

Mechanism of antagonist ligand binding to REV-ERBα.

REV-ERBα, a therapeutically promising nuclear hormone receptor, plays a crucial role in regulating various physiological processes such as the circadian clock, inflammation, and metabolism. However, the availability of chemical probes to investigate the pharmacology of this receptor is limited, with SR8278 being the only identified synthetic antagonist. Moreover, no X-ray crystal structures are currently available that demonstrate the binding of REV-ERBα to antagonist ligands. This lack of structural information impedes the development of targeted therapeutics. To address this issue, we employed Gaussian accelerated molecular dynamics (GaMD) simulations to investigate the binding pathway of SR8278 to REV-ERBα. For comparison, we also used GaMD to observe the ligand binding process of STL1267, for which an X-ray structure is available. GaMD simulations successfully captured the binding of both ligands to the receptor's orthosteric site and predicted the ligand binding pathway and important amino acid residues involved in the antagonist SR8278 binding. This study highlights the effectiveness of GaMD in investigating protein-ligand interactions, particularly in the context of drug recognition for nuclear hormone receptors.

Circadian rhythm mechanism in the suprachiasmatic nucleus and its relation to the olfactory system.

Animals need sleep, and the suprachiasmatic nucleus, the center of the circadian rhythm, plays an important role in determining the timing of sleep. The main input to the suprachiasmatic nucleus is the retinohypothalamic tract, with additional inputs from the intergeniculate leaflet pathway, the serotonergic afferent from the raphe, and other hypothalamic regions. Within the suprachiasmatic nucleus, two of the major subtypes are vasoactive intestinal polypeptide (VIP)-positive neurons and arginine-vasopressin (AVP)-positive neurons. VIP neurons are important for light entrainment and synchronization of suprachiasmatic nucleus neurons, whereas AVP neurons are important for circadian period determination. Output targets of the suprachiasmatic nucleus include the hypothalamus (subparaventricular zone, paraventricular hypothalamic nucleus, preoptic area, and medial hypothalamus), the thalamus (paraventricular thalamic nuclei), and lateral septum. The suprachiasmatic nucleus also sends information through several brain regions to the pineal gland. The olfactory bulb is thought to be able to generate a circadian rhythm without the suprachiasmatic nucleus. Some reports indicate that circadian rhythms of the olfactory bulb and olfactory cortex exist in the absence of the suprachiasmatic nucleus, but another report claims the influence of the suprachiasmatic nucleus. The regulation of circadian rhythms by sensory inputs other than light stimuli, including olfaction, has not been well studied and further progress is expected.

Comparison of choroidal thickness and choroidal vascular index in normotensive dippers and nondippers.

OBJECTIVE: The aim of this study was to evaluate the choroidal thickness and choroidal vascular index in normotensive individuals with dipping and nondipping patterns. METHODS: Patients who applied to the cardiology clinic for routine checkups and underwent 24-h blood pressure monitoring were included in our study. They were divided into two groups based on their dipper status. The patients in whom systolic blood pressure decreased during the nocturnal time by 10% or more of the daily blood pressure were defined as dippers. On the contrary, patients whose nocturnal systolic blood pressure decreased by less than 10% were defined as nondippers. Choroidal thickness and choroidal vascular index were measured by spectral-domain optical coherence tomography. Central macular thickness, retinal nerve fiber layer, and ganglion cell layer (GCL) analyses were also recorded. RESULTS: In total, 35 patients with dipper pattern and 34 patients with nondipper pattern were recruited. The mean subfoveal choroidal thickness was 349.72±90 µm in the dipper group and 358.54±132.5 µm in the nondipper group. The groups had no significant difference in choroidal thickness, central macular thickness, retinal nerve fiber layer, and ganglion cell layer analyses. However, the choroidal vascular index was statistically significantly lower in the nondipper group when compared to the dipper group (0.61±0.02 vs. 0.64±0.02; p<0.001). Also, the choroidal vascular index was negatively correlated with subfoveal choroidal thickness in the nondipper group (Spearman; r=-0.419; p=0.033). CONCLUSION: Our study showed that the choroidal vascular index was significantly lower in nondippers than in dippers. Nondipper individuals may be affected by vascular dysregulation, leading to alterations in the choroidal circulation.

Chrononutrition in the Prevention and Management of Metabolic Disorders: A Literature Review.

BACKGROUND: The concept of time-restricted eating (TRE) or time-restricted feeding (TRF) promotes daily periods of feeding and fasting to determine whole-body physiology. Chronic misalignment of circadian rhythms or chrono-disruption is related to an increased risk of diverse metabolic disorders. The progression of non-communicable diseases seems to be affected by the timing of meals. As a result, intermittent fasting is a promising approach for their management. The aim of the present literature review is to examine and scrutinize the TRE protocols in the fields of prevention and management of metabolic disorders. METHODS: This is a thorough literature review of the reported associations among circadian rhythm, metabolic disorders, diabetes mellitus, obesity, TRE, TRF, dietary habits, circadian disruption, cardiovascular diseases, atherosclerosis, and non-alcoholic fatty liver to find the already existing clinical studies from the last decade (2014-2024) in the most precise scientific online databases, using relevant specific keywords. Several inclusion and exclusion criteria were applied to scrutinize only longitudinal, cross-sectional, descriptive, and prospective clinical human studies. RESULTS: The currently available clinical findings remain scarce and suggest that chrononutrition behaviors such as TRE or TRF may promote several metabolic benefits, mainly in body weight control and fat loss. Improvements in glucose levels and lipid profiles are currently quite controversial since some clinical studies show little or no effect. As far as liver diseases are concerned, the efficacy of intermittent fasting seems to be stronger in the management of non-alcoholic fatty liver disease due to body weight decline and fat loss. CONCLUSIONS: Even if there has been a gradual increase in clinical studies in the last few years, providing promising perspectives, currently, there is no conclusive evidence for the role of chrononutrition in metabolic disorders. Future studies should be well-designed with longer duration and larger sample sizes. Moreover, it is important to examine the best timing of the eating window and its feasibility.

Chrononutrition in traditional European medicine-Ideal meal timing for cardiometabolic health promotion.

Meal timing plays a crucial role for cardiometabolic health, given the circadian regulation of cardiometabolic function. However, to the best of our knowledge, no concept of meal timing exists in traditional European medicine (TEM). Therefore, in this narrative review, we aim to define the optimal time slot for energy intake and optimal energy distribution throughout the day in a context of TEM and explore further implications. By reviewing literature published between 2002 and 2022, we found that optimal timing for energy intake may be between 06:00 and 09:00, 12:00 and 14:00, and between 15:00 and 18:00, with high energy breakfast, medium energy lunch and low energy dinner and possibly further adjustments according to one's chronotype and genetics. Also, timing and distribution of energy intake may serve as a novel therapeutic strategy to optimize coction, a concept describing digestion and metabolism in TEM. Please cite this article as: Eberli NS, Colas L, Gimalac A. Chrononutrition in traditional European medicine-Ideal meal timing for cardiometabolic health promotion. J Integr Med. 2024; 22(2);115-125.

Social jet lag impairs exercise volume and attenuates physiological and metabolic adaptations to voluntary exercise training.

Social jet lag (SJL) is a misalignment between sleep and wake times on workdays and free days. SJL leads to chronic circadian rhythm disruption and may affect nearly 70% of the general population, leading to increased risk for cardiometabolic diseases. This study investigated the effects of SJL on metabolic health, exercise performance, and exercise-induced skeletal muscle adaptations in mice. Ten-week-old C57BL/6J mice (n = 40) were allocated to four groups: control sedentary (CON-SED), control exercise (CON-EX), social jet lag sedentary (SJL-SED), and social jet lag exercise (SJL-EX). CON mice were housed under a 12:12-h light-dark cycle. SJL was simulated by implementing a 4-h phase delay for 3 days to simulate "weekends," followed by a 4-h phase advance back to "weekdays," for 6 wk. EX mice had free access to a running wheel. Graded exercise tests (GXTs) and glucose tolerance tests (GTTs) were performed at baseline and after intervention to monitor the effects of exercise and social jet lag on cardiorespiratory and metabolic health, respectively. SJL led to alterations in activity and running patterns and clock gene expression in skeletal muscle and decreased average running distance (P < 0.05). SJL-SED mice gained significantly more weight compared with CON-SED and SJL-EX mice (P < 0.01). SJL impaired fasting blood glucose and glucose tolerance compared with CON mice (P < 0.05), which was partially restored by exercise in SJL-EX mice. SJL also blunted improvements in exercise performance and mitochondrial content in the quadriceps. These data suggest that SJL blunted some cardiometabolic adaptations to exercise and that proper circadian hygiene is necessary for maintaining health and performance.NEW & NOTEWORTHY In mice, disrupting circadian rhythms with social jet lag for 6 wk caused significant weight gain, higher fasting blood glucose, and impaired glucose tolerance compared with control. Voluntary exercise in mice experiencing social jet lag prevented weight gain, though the mice still experienced increased fasting blood glucose and impaired exercise performance compared with trained mice not experiencing social jet lag. Social jet lag seems to be a potent circadian rhythm disruptor that impacts exercise-induced training adaptations.

Association between nocturnal blood pressure phenotype and adverse cardiovascular prognosis in patients with coronary heart disease and hypertension.

Nocturnal blood pressure and nighttime dipping patterns are associated with the occurrence of cardiovascular events. However, there is few research on whether riser pattern is associated with the poor prognosis of patients with coronary heart disease (CHD) and hypertension independent of nighttime systolic blood pressure (SBP). This prospective and observational clinical study included 568 hospitalized patients with CHD and hypertension. All patients underwent 24-h ambulatory blood pressure (BP) monitoring during their hospitalization. Multivariate adjusted Cox proportional hazard models were utilized to examine the associations of nocturnal blood pressure and dipping status with primary endpoint events. Additionally, Harrell's C-statistics were employed to compare the discriminative ability of each model. During the 1-year follow-up period, 64 (11.3%) primary endpoint events were recorded, including 55 (9.7%) atherosclerotic cardiovascular disease (ASCVD) events. After adjusting for demographic and clinical risk variables, nighttime SBP was significantly related to the risk of incident primary endpoint events [per 20 mm Hg increase: hazard ratio (HR) = 1.775, 95% confidence interval (CI) 1.256-2.507]. The riser pattern group exhibited a significantly higher risk for primary endpoint events compared to the dipper pattern group, even after adjusting for office SBP (HR: 2.687, 95% CI: 1.015-7.110, p = .047). Furthermore, the addition of nighttime SBP or dipping status to the base model yielded statistically significant increments in C-statistic values (p = .036 and p = .007). However, adding both nighttime SBP and dipping status did not significantly enhance the model's performance in predicting the risk of primary endpoint events and ASCVD events according to the C-index (p = .053 and p = .054), which meant that the riser pattern group did not exhibit a significantly higher risk for primary endpoint events compared to the dipper pattern group after adjusting for nighttime SBP. In conclusion, nocturnal SBP and riser pattern demonstrated an association with adverse prognosis in patients with CHD and hypertension. Notably, nocturnal SBP proved to be a more reliable predictor than dipping status.

Autophagy as a new player in the regulation of clock neurons physiology of Drosophila melanogaster.

Axonal terminals of the small ventral lateral neurons (sLNvs), the circadian clock neurons of Drosophila, show daily changes in their arborization complexity, with many branches in the morning and their shrinkage during the night. This complex phenomenon is precisely regulated by several mechanisms. In the present study we describe that one of them is autophagy, a self-degradative process, also involved in changes of cell membrane size and shape. Our results showed that autophagosome formation and processing in PDF-expressing neurons (both sLNv and lLNv) are rhythmic and they have different patterns in the cell bodies and terminals. These rhythmic changes in the autophagy activity seem to be important for neuronal plasticity. We found that autophagosome cargos are different during the day and night, and more proteins involved in membrane remodeling are present in autophagosomes in the morning. In addition, we described for the first time that Atg8-positive vesicles are also present outside the sLNv terminals, which suggests that secretory autophagy might be involved in regulating the clock signaling network. Our data indicate that rhythmic autophagy in clock neurons affect the pacemaker function, through remodeling of terminal membrane and secretion of specific proteins from sLNvs.

Recommendations for measuring and standardizing light for laboratory mammals to improve welfare and reproducibility in animal research.

Light enables vision and exerts widespread effects on physiology and behavior, including regulating circadian rhythms, sleep, hormone synthesis, affective state, and cognitive processes. Appropriate lighting in animal facilities may support welfare and ensure that animals enter experiments in an appropriate physiological and behavioral state. Furthermore, proper consideration of light during experimentation is important both when it is explicitly employed as an independent variable and as a general feature of the environment. This Consensus View discusses metrics to use for the quantification of light appropriate for nonhuman mammals and their application to improve animal welfare and the quality of animal research. It provides methods for measuring these metrics, practical guidance for their implementation in husbandry and experimentation, and quantitative guidance on appropriate light exposure for laboratory mammals. The guidance provided has the potential to improve data quality and contribute to reduction and refinement, helping to ensure more ethical animal use.

Diel Cycle Proteomics: Illuminating Molecular Dynamics in Purple Bacteria for Optimized Biotechnological Applications.

Circadian rhythms, characterized by approximately 24 h cycles, play a pivotal role in enabling various organisms to synchronize their biological activities with daily variations. While ubiquitous in Eukaryotes, circadian clocks remain exclusively characterized in Cyanobacteria among Prokaryotes. These rhythms are regulated by a core oscillator, which is controlled by a cluster of three genes: kaiA, kaiB, and kaiC. Interestingly, recent studies revealed rhythmic activities, potentially tied to a circadian clock, in other Prokaryotes, including purple bacteria such as Rhodospirillum rubrum, known for its applications in fuel and plastic bioproduction. However, the pivotal question of how light and dark cycles influence protein dynamics and the expression of putative circadian clock genes remains unexplored in purple non-sulfur bacteria. Unraveling the regulation of these molecular clocks holds the key to unlocking optimal conditions for harnessing the biotechnological potential of R. rubrum. Understanding how its proteome responds to different light regimes-whether under continuous light or alternating light and dark cycles-could pave the way for precisely fine-tuning bioproduction processes. Here, we report for the first time the expressed proteome of R. rubrum grown under continuous light versus light and dark cycle conditions using a shotgun proteomic analysis. In addition, we measured the impact of light regimes on the expression of four putative circadian clock genes (kaiB1, kaiB2, kaiC1, kaiC2) at the transcriptional and translational levels using RT-qPCR and targeted proteomic (MRM-MS), respectively. The data revealed significant effects of light conditions on the overall differential regulation of the proteome, particularly during the early growth stages. Notably, several proteins were found to be differentially regulated during the light or dark period, thus impacting crucial biological processes such as energy conversion pathways and the general stress response. Furthermore, our study unveiled distinct regulation of the four kai genes at both the mRNA and protein levels in response to varying light conditions. Deciphering the impact of the diel cycle on purple bacteria not only enhances our understanding of their ecology but also holds promise for optimizing their applications in biotechnology, providing valuable insights into the origin and evolution of prokaryotic clock mechanisms.

The Trissin/TrissinR signaling pathway in the circadian network regulates evening activity in Drosophila melanogaster under constant dark conditions.

The circadian clock in Drosophila is governed by a neural network comprising approximately 150 neurons, known as clock neurons, which are intricately interconnected by various neurotransmitters. The neuropeptides that play functional roles in these clock neurons have been identified; however, the roles of some neuropeptides, such as Trissin, remain unclear. Trissin is expressed in lateral dorsal clock neurons (LNds), while its receptor, TrissinR, is expressed in dorsal neuron 1 (DN1) and LNds. In this study, we investigated the role of the Trissin/TrissinR signaling pathway within the circadian network in Drosophila melanogaster. Analysis involving our newly generated antibody against the Trissin precursor revealed that Trissin expression in the LNds cycles in a circadian manner. Behavioral analysis further demonstrated that flies with Trissin or TrissinR knockout or knockdown showed delayed evening activity offset under constant darkness conditions. Notably, this observed delay in evening activity offset in TrissinRNAi flies was restored via the additional knockdown of Ion transport peptide (ITP), indicating that the Trissin/TrissinR signaling pathway transmits information via ITP. Therefore, this pathway may be a key regulator of the timing of evening activity offset termination, orchestrating its effects in collaboration with the neuropeptide, ITP.

Circadian variations in the elderly: A scoping review.

The circadian clock plays important roles in several physiological processes. With aging, some of these circadian rhythms have been shown to be disrupted and suggested contributing to age-related diseases. The aim of this scoping review was to examine and map the existing evidence of circadian differences between young and older people in body fluid composition. Literature search was carried out on PubMed, Embase, Scopus and OpenGrey. The studies were screened based on inclusion and exclusion criteria by two independent reviewers and the results were summarized tabularly and narratively. The review process resulted in the identification of 1889 publications, of which 42 were eligible for inclusion. Forty-eight parameters or families of parameters were identified, including cortisol and melatonin, sex hormones, thyroid-related hormones, steroids and aldosterone. However, many were reported by only a single study. The results from the studies were heterogeneous. Even though the majority suggested the flattening of several circadian oscillations in the elderly population, this was not always observed for all the parameters analyzed, and some contradictory results were found. This review revealed a substantial number of publications that explored this research question, but further studies would be important to elucidate the clinical significance of these alterations.

Circadian patterns and photoperiodic modulation of clock gene expression and neuroendocrine hormone secretion in the marine teleost Larimichthys crocea.

The light/dark cycle, known as the photoperiod, plays a crucial role in influencing various physiological activities in fish, such as growth, feeding and reproduction. However, the underlying mechanisms of this influence are not fully understood. This study focuses on exploring the impact of different light regimes (LD: 12 h of light and 12 h of darkness; LL: 24 h of light and 0 h of darkness; DD: 0 h of light and 24 h of darkness) on the expression of clock genes (LcClocka, LcClockb, LcBmal, LcPer1, LcPer2) and the secretion of hormones (melatonin, GnRH, NPY) in the large yellow croaker, Larimichthys crocea. Real-time quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assays were utilized to assess how photoperiod variations affect clock gene expression and hormone secretion. The results indicate that changes in photoperiod can disrupt the rhythmic patterns of clock genes, leading to phase shifts and decreased expression. Particularly under LL conditions, the pineal LcClocka, LcBmal and LcPer1 genes lose their rhythmicity, while LcClockb and LcPer2 genes exhibit phase shifts, highlighting the importance of dark phase entrainment for maintaining rhythmicity. Additionally, altered photoperiod affects the neuroendocrine system of L. crocea. In comparison to the LD condition, LL and DD treatments showed a phase delay of GnRH secretion and an acceleration of NPY synthesis. These findings provide valuable insights into the regulatory patterns of circadian rhythms in fish and may contribute to optimizing the light environment in the L. crocea farming industry.

Intrauterine and early-life malnutrition in rats disrupts the circadian rhythm programming of energy metabolites through adulthood.

Maternal malnutrition plays a crucial role in functional development, resulting in behavioral, cognitive, and metabolic abnormalities and disturbances. "Cafeteria diet" has been linked to obesity, metabolic syndrome, diabetes, and other metabolic disruptions in the mammalian lifespan. However, there are very few reports about the effect of intrauterine and early postnatal malnutrition on the circadian rhythm programming of energy metabolites. In mammals, circadian rhythm central control is fundamental for correct interaction with the environment and physiological regulation. Exposure to malnutrition during development imprints metabolic programming throughout life on the central nervous system and peripheral systems. Lifespan studies exploring the effect of high fat/low protein diet administered during critical periods of development are scarce. The present study explored the effect of intrauterine and perinatal malnutrition induced by a high fat/low protein diet (Cafeteria Diet) on circadian and peripheral oscillators controlling glucose, insulin, and triglycerides in rats at 40 and 90 days of age. We evaluated plasma glucose and triglyceride levels in 6 Zeitgeber times, in addition to an intraperitoneal glucose tolerance test (IpTGT) and homeostasis model assessment of insulin resistance (HOMA-IR) at two time-points over 24h. Our results show that offspring of malnourished dams fed cafeteria diet present alterations in circadian rhythmicity of glucose and triglycerides associated with a change in glucose tolerance and insulin sensibility differentially regulated at the development stage and time of day. Intrauterine and early malnutrition due to a cafeteria diet produces maladaptive responses and programs energetic metabolism at several developmental stages during the lifespan.