Entrainment Of Circadian Rhythms Research Articles

Dim light at night unmasks sex-specific differences in circadian and autonomic regulation of cardiovascular physiology

Shift work and artificial light at night disrupt the entrainment of endogenous circadian rhythms in physiology and behavior to the day-night cycle. We hypothesized that exposure to dim light at night (dLAN) disrupts feeding rhythms, leading to sex-specific changes in autonomic signaling and day-night heart rate and blood pressure rhythms. Compared to mice housed in 12-hour light/12-hour dark cycles, mice exposed to dLAN showed reduced amplitudes in day-night feeding, heart rate, and blood pressure rhythms. In female mice, dLAN reduced the amplitude of day-night cardiovascular rhythms by decreasing the relative sympathetic regulation at night, while in male mice, it did so by increasing the relative sympathetic regulation during the daytime. Time-restricted feeding to the dim light cycle reversed these autonomic changes in both sexes. We conclude that dLAN induces sex-specific changes in autonomic regulation of heart rate and blood pressure, and time-restricted feeding may represent a chronotherapeutic strategy to mitigate the cardiovascular impact of light at night.

OpsinLW2 serves as a circadian photoreceptor in the entrainment of circadian locomotor rhythm of a firebrat

Photic entrainment is an essential function of the circadian clock, which enables organisms to set the appropriate timing of daily behavioral and physiological events. Recent studies have shown that the mechanisms of the circadian clock and photic entrainment vary among insect species. This study aimed to elucidate the circadian photoreceptors necessary for photic entrainment in firebrats Thermobia domestica, one of the most primitive apterygote insects. A homology search of publicly available RNA sequence (RNA-seq) data from T. domestica exhibited a cryptochrome 2 (cry2) gene and three opsin genes, opsin long wavelength 1 (opLW1), opLW2, and opUV, as candidate circadian photoreceptors. We examined the possible involvement of these genes in photic entrainment of firebrat locomotor rhythms. Firebrats had the highest entrainability to the light–dark cycle of green light. Treatment with dsRNA of the candidate genes strongly downregulated the respective targeted genes, and in the case of opsin genes, other untargeted genes were occasionally downregulated to various degrees. Under constant light, most control firebrats became arrhythmic, whereas a fraction of those treated with double RNAi of the two opLWs remained rhythmic. Behavioral experiments revealed that the transient cycles necessary for re-entrainment to shifted light cycles were lengthened when opLW2 expression was reduced. These results suggest that opLW2 is involved in the photic entrainment of circadian rhythm in firebrats.

The circadian molecular clock in the suprachiasmatic nucleus is necessary but not sufficient for fear entrainment

We show that nocturnal aversive stimuli presented to mice while they are eating and drinking outside of their safe nest can entrain circadian behaviors, leading to a shift toward daytime activity. We also show that the canonical molecular circadian clock is necessary for fear entrainment and that an intact molecular clockwork in the suprachiasmatic nucleus, the site of the central circadian pacemaker, is necessary but not sufficient to sustain fear entrainment of circadian rhythms. Our results demonstrate that entrainment of a circadian clock by cyclic fearful stimuli can lead to severely mistimed circadian behavior that persists even after the aversive stimulus is removed. Together, our findings support the interpretation that circadian and sleep symptoms associated with fear and anxiety disorders are, in part, the output of a fear-entrained clock, and provide a mechanistic insight into this clock.

Addressing Circadian Disruptions in Visually Impaired Paralympic Athletes.

Transmeridian travel is common for elite athletes participating in competitions and training. However, this travel can lead to circadian misalignment wherein the internal biological clock becomes desynchronized with the light-dark cycle of the new environment, resulting in performance decrement and potential negative health consequences. Existing literature extensively discusses recommendations for managing jet lag, predominantly emphasizing light-based interventions to synchronize the internal clock with the anticipated time at the destination. Nevertheless, visually impaired (VI) athletes may lack photoreceptiveness, diminishing or nullifying the effectiveness of this therapy. Consequently, this invited commentary explores alternative strategies for addressing jet lag in VI athletes. VI athletes with light perceptionbut reduced visual acuity or visual fields may still benefit from light interventions in managing jet lag. However, VI athletes lacking a conscious perception of light should rely on gradual shifts in behavioral factors, such as meal timing and exercise, to facilitate the entrainment of circadian rhythms to the destination time. Furthermore, interventions like melatonin supplementation may prove useful during and after travel. In addition, it is recommended that athlete guides adopt phase-forward or phase-back approaches to synchronize with the athlete, aiding in jet-lag management and optimizing performance.

A structural decryption of cryptochromes.

Cryptochromes (CRYs), which are signaling proteins related to DNA photolyases, play pivotal roles in sensory responses throughout biology, including growth and development, metabolic regulation, circadian rhythm entrainment and geomagnetic field sensing. This review explores the evolutionary relationships and functional diversity of cryptochromes from the perspective of their molecular structures. In general, CRY biological activities derive from their core structural architecture, which is based on a Photolyase Homology Region (PHR) and a more variable and functionally specific Cryptochrome C-terminal Extension (CCE). The α/β and α-helical domains within the PHR bind FAD, modulate redox reactive residues, accommodate antenna cofactors, recognize small molecules and provide conformationally responsive interaction surfaces for a range of partners. CCEs add structural complexity and divergence, and in doing so, influence photoreceptor reactivity and tailor function. Primary and secondary pockets within the PHR bind myriad moieties and collaborate with the CCEs to tune recognition properties and propagate chemical changes to downstream partners. For some CRYs, changes in homo and hetero-oligomerization couple to light-induced conformational changes, for others, changes in posttranslational modifications couple to cascades of protein interactions with partners and effectors. The structural exploration of cryptochromes underscores how a broad family of signaling proteins with close relationship to light-dependent enzymes achieves a wide range of activities through conservation of key structural and chemical properties upon which function-specific features are elaborated.

Time-Optimal Circadian Rhythm Entrainment Is Not Robust

Time-Optimal Circadian Rhythm Entrainment Is Not Robust

Effect of light exposure on circadian rhythm in theront excystment in Cryptocaryon irritans

We examined the effects of light exposure on the theront excystment circadian rhythm in Cryptocaryon irritans using a newly invented apparatus, which enabled us to examine the excystment rhythms of theronts from tomonts with low labor. Using the apparatus, we examined the timings of theront excystment from tomonts exposed directly to light and from tomonts exposed to light-exposed seawater by counting the number of excysted theronts. We found that the theront excystment time changed only when tomonts were directly exposed to light, indicating that light reception is essential for circadian rhythm entrainment. When tomonts were exposed to light only once for 12 h, either on Day 1, Day 2, or Day 3 after leaving host and being encysted, the circadian rhythm was entrained according to the photoperiod given on tomonts. Tomonts exposed to a low light (1 lx) with 12L:12D photoperiod daily showed a circadian rhythm similar to that in tomonts exposed to an intense light (500 lx) under the same photoperiod. When tomonts were incubated at 22 °C, 25 °C, or 28 °C under the same photoperiod, almost the same circadian rhythm was developed, suggesting temperature has little effect on the circadian rhythm entrainment between the range, even though the date of excystment was delayed in lower temperatures. These results suggest the circadian rhythm of theront excystment can be entrained in tomonts on the seabed of inner bays where net–cage aquaculture is conducted, and be involved in the outbreaks of cryptocaryoniasis there.

Effects of melatonin on dopaminergic neuron development via IP3-mediated mitochondrial Ca2+ regulation in autism spectrum disorder

Melatonin entrainment of suprachiasmatic nucleus-regulating circadian rhythms is mediated by MT1 and MT2 receptors. Melatonin also has neuroprotective and mitochondrial activating effects, suggesting it may affect neurodevelopment. We studied melatonin's pharmacological effects on autism spectrum disorder (ASD) neuropathology. Deciduous tooth-derived stem cells from children with ASD were used to model neurodevelopmental defects and differentiated into dopaminergic neurons (ASD-DNs) with or without melatonin. Without melatonin, ASD-DNs had reduced neurite outgrowth, mitochondrial dysfunction, lower mitochondrial Ca2+ levels, and Ca2+ accumulation in the endoplasmic reticulum (ER) compared to control DNs from typically developing children-derived stem cells. Melatonin enhanced IP3-dependent Ca2+ release from ER to mitochondria, improving mitochondrial function and neurite outgrowth in ASD-DNs. Luzindole, an MT1/MT2 antagonist, blocked these effects. Thus, melatonin supplementation may improve dopaminergic system development in ASD by modulating mitochondrial Ca2+ homeostasis via MT1/MT2 receptors.

Robustness of Optimal Circadian Rhythm Entrainment under Model Perturbation.

The optimal circadian rhythm entrainment problem has been studied based on mathematical models, e.g. the Kronauer model. In this paper, we study the robustness of light-based circadian rhythm entrainment under model parameter perturbations as well as propose a feedback control law to improve the robustness of the entrainment strategy. Our study finds the model parameter whose perturbations affect the entrainment the most. We also find that feedback control reduces the sensivitity of the entrainment process to model parameter perturbations.Clinical relevance- Circadian misalignment has negative impacts on health, such as higher risks of cardiovascular disease and cancer. We present a numerical study of how well optimized circadian rhythm entrainment plans that are derived from a generic mathematical model work on personalized cases.

Effects of the timing of protein infusion on the daily rhythms of milk synthesis and plasma hormones and metabolites in dairy cows

Milk synthesis exhibits a daily rhythm that is modified by the timing of feed intake. However, it is unknown how specific nutrients entrain this daily rhythm. Amino acids have an important role in milk synthesis, and may have a role in entrainment of mammary circadian rhythms. The objective of this study was to determine the effects of intestinally absorbed protein on daily rhythms of milk and milk component synthesis and key plasma hormones and metabolites. Nine lactating Holstein cows were assigned to 1 of 3 treatment sequences in a 3 × 3 Latin square. Treatments included abomasal infusions of 500 g/d of sodium caseinate either continuously throughout the day (CON), for 8 h/d from 0900 to 1700 h (DAY), or for 8 h/d from 2100 to 0500 h (NGT). Cows were milked every 6 h during the final 8 d of each period. A 24-h rhythm was fit to data using cosine analysis and the amplitude and acrophase were determined. Night infusion of protein decreased the daily milk yield and milk protein yield by 8.2% and 9.2%, respectively. Milk fat yield was increased 5.5% by DAY and milk fat concentration was increased 8.8% by NGT. Milk yield exhibited a daily rhythm in all treatments, with NGT increasing the amplitude of the daily rhythm 33% compared with CON. Milk fat concentration fit a daily rhythm in CON and NGT, but not DAY, whereas milk protein concentration fit a daily rhythm in CON and DAY, but not NGT. Moreover, DAY abolished the daily rhythm of plasma glucose concentration, but induced rhythms of plasma insulin and nonesterified fatty acid concentrations. Results suggest that feeding increased protein levels during the early part of the day may increase milk fat yield and modify energy metabolism through increased daily variation in insulin-stimulated lipid release, but additional research focused on feeding multiple diets across the day is required.

Wide Range CCT Laser-Based Illuminant With High Efficiency and Excellent Optical Performances

A wide range correlated color temperature (CCT) white light laser-based illuminant (LBI) consisting of dual blue laser diodes (LDs), yellow phosphor color converters and red LDs has been proposed. In addition to the conventional 455 nm blue LDs-pumped phosphor color converters, another blue LD is utilized for the adjustment of CCT and improvement of the color rendering index (CRI). Considering systematic manipulation of the power ratio of LDs and peak wavelength of tuning blue LDs from 440 nm to 480 nm, different combinations of spectral power distributions of LBIs were simulated. It shows that an optimized 465 nm tuning blue LD is employed to achieve a balance between optical performances and blue light hazard efficiency of radiation (BLHER). The first practical LBI comprised of Y <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> Al <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sub> O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">12</sub> :Ce <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3+</sup> (YAG:Ce <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3+</sup> ) phosphor color converters and three monochromatic LDs of 455 nm, 465 nm and 635 nm was fabricated based on the stated simulations. In good agreement with the simulation results, the LBI has simultaneously achieved an excellent CRI beyond 85, a high luminous flux of approximately 2000 lm and a high luminous efficiency of radiation (LER) of over 300 lm/W at the fairly wide CCT range of 3300 K to 6000 K. The low BLHER was consistently below 0.237. The circadian action factor (CAF) was between 0.36 and 0.83, and its tunability was 2.31 above the CCT range, which favors the entrainment of circadian rhythm. Therefore, this work demonstrates a promising method for providing high-quality and human-oriented white light sources in applications requiring great brightness.

Sensory conflict disrupts circadian rhythms in the sea anemone Nematostella vectensis.

Circadian clocks infer time of day by integrating information from cyclic environmental factors called zeitgebers, including light and temperature. Single zeitgebers entrain circadian rhythms, but few studies have addressed how multiple, simultaneous zeitgeber cycles interact to affect clock behavior. Misalignment between zeitgebers ('sensory conflict') can disrupt circadian rhythms, or alternatively clocks may privilege information from one zeitgeber over another. Here, we show that temperature cycles modulate circadian locomotor rhythms in Nematostella vectensis, a model system for cnidarian circadian biology. We conduct behavioral experiments across a comprehensive range of light and temperature cycles and find that Nematostella's circadian behavior is disrupted by chronic misalignment between light and temperature, which involves disruption of the endogenous clock itself rather than a simple masking effect. Sensory conflict also disrupts the rhythmic transcriptome, with numerous genes losing rhythmic expression. However, many metabolic genes remained rhythmic and in-phase with temperature, and other genes even gained rhythmicity, implying that some rhythmic metabolic processes persist even when behavior is disrupted. Our results show that a cnidarian clock relies on information from light and temperature, rather than prioritizing one signal over the other. Although we identify limits to the clock's ability to integrate conflicting sensory information, there is also a surprising robustness of behavioral and transcriptional rhythmicity.

Is obstructive sleep apnea a circadian rhythm disorder?

Obstructive sleep apnea is the most common sleep-related breathing disorder worldwide and remains underdiagnosed. Its multiple associated comorbidities contribute to a decreased quality of life and work performance as well as an increased risk of death. Standard treatment seems to have limited effects on cardiovascular and metabolic aspects of the disease, emphasising the need for early diagnosis and additional therapeutic approaches. Recent evidence suggests that the dysregulation of circadian rhythms, processes with endogenous rhythmicity that are adjusted to the environment through various cues, is involved in the pathogenesis of comorbidities. In patients with obstructive sleep apnea, altered circadian gene expression patterns have been demonstrated. Obstructive respiratory events may promote circadian dysregulation through the effects of sleep disturbance and intermittent hypoxia, with subsequent inflammation and disruption of neural and hormonal homeostasis. In this review, current knowledge on obstructive sleep apnea, circadian rhythm regulation, and circadian rhythm sleep disorders is summarised. Studies that connect obstructive sleep apnea to circadian rhythm abnormalities are critically evaluated. Furthermore, pathogenetic mechanisms that may underlie this association, most notably hypoxia signalling, are presented. A bidirectional relationship between obstructive sleep apnea and circadian rhythm dysregulation is proposed. Approaching obstructive sleep apnea as a circadian rhythm disorder may prove beneficial for the development of new, personalised diagnostic, therapeutic and prognostic tools. However, further studies are needed before the clinical approach to obstructive sleep apnea includes targeting the circadian system.

Nonphotic entrainment of central and peripheral circadian clocks in mice by scheduled voluntary exercise under constant darkness.

In mammals, the central circadian pacemaker in the suprachiasmatic nucleus (SCN) entrains to an environmental light-dark (LD) cycle and organizes the temporal order of circadian rhythms in physiology and behavior. Previously, some studies have demonstrated that scheduled exercise could entrain the free-running behavior rhythm in nocturnal rodents. However, it remains unknown whether entrainment by scheduled exercise alters the internal temporal order of the behavioral circadian rhythms or clock gene expression in the SCN, extra-SCN brain regions, and peripheral organs when mice are entrained to the scheduled exercise under constant darkness (DD). In the present study, we examined circadian rhythms in locomotor activity and clock gene Per1 expression by bioluminescence reporter (Per1-luc) in the SCN, arcuate nucleus (ARC), liver, and skeletal muscle of mice entrained to an LD cycle, mice free-running under DD, and mice entrained to daily exposure to a new cage with a running wheel (NCRW) under DD. All mice showed a steady-state entrainment of behavioral circadian rhythms to NCRW exposure under DD in parallel with shortening of the α when compared with that under DD. The temporal order of behavioral circadian rhythms and the Per1-luc rhythms in the SCN and peripheral tissues but not in the ARC were maintained in the mice entrained to the NCRW and LD cycles; in contrast, the temporal order was altered in the mice under DD. The present findings reveal that the SCN entrains to daily exercise, and daily exercise reorganizes the internal temporal order of behavioral circadian rhythms and clock gene expression in the SCN and peripheral tissues.

Circadian rhythm entrainment of the jewel wasp, Nasonia vitripennis, by antagonistic interactions of multiple spectral inputs.

Circadian light entrainment in some insects is regulated by blue-light-sensitive cryptochrome (CRY) protein that is expressed in the clock neurons, but this is not the case in hymenopterans. The hymenopteran clock does contain CRY, but it appears to be light-insensitive. Therefore, we investigated the role of retinal photoreceptors in the photic entrainment of the jewel wasp Nasonia vitripennis. Application of monochromatic light stimuli at different light intensities caused phase shifts in the wasp's circadian activity from which an action spectrum with three distinct peaks was derived. Electrophysiological recordings from the compound eyes and ocelli revealed the presence of three photoreceptor classes, with peak sensitivities at 340 nm (ultraviolet), 450 nm (blue) and 530 nm (green). An additional photoreceptor class in the ocelli with sensitivity maximum at 560-580 nm (red) was found. Whereas a simple sum of photoreceptor spectral sensitivities could not explain the action spectrum of the circadian phase shifts, modelling of the action spectrum indicates antagonistic interactions between pairs of spectral photoreceptors, residing in the compound eyes and the ocelli. Our findings imply that the photic entrainment mechanism in N. vitripennis encompasses the neural pathways for measuring the absolute luminance as well as the circuits mediating colour opponency.

Fbxl4 Regulates the Photic Entrainment of Circadian Locomotor Rhythms in the Cricket Gryllus bimaculatus.

Photic entrainment is an essential property of the circadian clock that sets the appropriate timing of daily behavioral and physiological events. However, the molecular mechanisms underlying the entrainment remain largely unknown. In the cricket Gryllus bimaculatus, the immediate early gene c-fosB plays an important role in photic entrainment, followed by a mechanism involving cryptochromes (crys). However, the association between c-fosB expression and crys remains unclear. In the present study, using RNA-sequencing analysis, we found that five Fbxl family genes (Fbxl4, Fbxl5, Fbxl16, Fbxl-like1, and Fbxl-like2) encoding F-box and leucine-rich repeat proteins are likely involved in the mechanism following light-dependent c-fosB induction. RNA interference (RNAi) of c-fosA/B significantly downregulated Fbxls expression, whereas RNAi of the Fbxl genes exerted no effect on c-fosB expression. The Fbxl genes showed rhythmic expression under light-dark cycles (LDs) with higher expression levels in early day (Fbxl16), whole day (Fbxl-like1), or day-to-early night (Fbxl4, Fbxl5, and Fbxl-like2), whereas their expression was reduced in the dark. We then examined the effect of their RNAi on the photic entrainment of the locomotor rhythm and found that RNAi of Fbxl4 either disrupted or significantly delayed the re-entrainment of the locomotor rhythm to shifted LDs. These results suggest that light-induced c-fosB expression stimulates Fbxl4 expression to reset the circadian clock.

Burning the candle at both ends: Intraretinal signaling of intrinsically photosensitive retinal ganglion cells.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are photoreceptors located in the ganglion cell layer. They project to brain regions involved in predominately non-image-forming functions including entrainment of circadian rhythms, control of the pupil light reflex, and modulation of mood and behavior. In addition to possessing intrinsic photosensitivity via the photopigment melanopsin, these cells receive inputs originating in rods and cones. While most research in the last two decades has focused on the downstream influence of ipRGC signaling, recent studies have shown that ipRGCs also act retrogradely within the retina itself as intraretinal signaling neurons. In this article, we review studies examining intraretinal and, in addition, intraocular signaling pathways of ipRGCs. Through these pathways, ipRGCs regulate inner and outer retinal circuitry through both chemical and electrical synapses, modulate the outputs of ganglion cells (both ipRGCs and non-ipRGCs), and influence arrangement of the correct retinal circuitry and vasculature during development. These data suggest that ipRGC function plays a significant role in the processing of image-forming vision at its earliest stage, positioning these photoreceptors to exert a vital role in perceptual vision. This research will have important implications for lighting design to optimize the best chromatic lighting environments for humans, both in adults and potentially even during fetal and postnatal development. Further studies into these unique ipRGC signaling pathways could also lead to a better understanding of the development of ocular dysfunctions such as myopia.

Relationship of Circadian Rhythm in Behavioral Characteristics and Lipid Peroxidation of Brain Tissues in Mice.

This study aimed to explore the relationship among several indices of circadian rhythms and lipid peroxidation of brain tissue in mice. After entrainment of 4-week-old mice, one group was disrupted their circadian rhythms for three days and the other group for seven days (n = 10, respectively). After a recovery period, the Y-maze test, the elevated plus maze test, the tail suspension test, and the forced swimming test were conducted. To assess lipid peroxidation in brain tissue, thiobarbituric acid reactive substances were measured in the cortex, hippocampus, and cerebellum. When circadian rhythms were disrupted and adapted back to their original rhythm, the recovery time of the 7-day disruption group (median 3.35 days) was significiantly faster than one of the 3-day disruption group (median 4.87 days). In the group with a 7-day disruption, mice that had recovered their rhythms early had higher malondialdehyde levels in their hippocampus compared to those with delayed recovery. The entrainment of circadian rhythms was negatively correlated with the malondialdehyde level of brain tissue. The behavioral test results showed no differences depending on the disruption durations or recovery patterns of circadian rhythms. These results suggest that disruption types, recovery patterns, and the entrainment of circadian rhythms are likely to affect oxidative stress in adolescents or young adult mice. Future study is needed to confirm and specify these results on the effects of circadian rhythms on oxidative stress and age-dependent effects.

Dpr10 and Nocte are required for Drosophila motor axon pathfinding

The paths axons travel to reach their targets and the subsequent synaptic connections they form are highly stereotyped. How cell surface proteins (CSPs) mediate these processes is not completely understood. The Drosophila neuromuscular junction (NMJ) is an ideal system to study how pathfinding and target specificity are accomplished, as the axon trajectories and innervation patterns are known and easily visualized. Dpr10 is a CSP required for synaptic partner choice in the neuromuscular and visual circuits and for axon pathfinding in olfactory neuron organization. In this study, we show that Dpr10 is also required for motor axon pathfinding. To uncover how Dpr10 mediates this process, we used immunoprecipitation followed by mass spectrometry to identify Dpr10 associated proteins. One of these, Nocte, is an unstructured, intracellular protein implicated in circadian rhythm entrainment. We mapped nocte expression in larvae and found it widely expressed in neurons, muscles, and glia. Cell-specific knockdown suggests nocte is required presynaptically to mediate motor axon pathfinding. Additionally, we found that nocte and dpr10 genetically interact to control NMJ assembly, suggesting that they function in the same molecular pathway. Overall, these data reveal novel roles for Dpr10 and its newly identified interactor, Nocte, in motor axon pathfinding and provide insight into how CSPs regulate circuit assembly.

Nutritional entrainment of circadian rhythms under alignment and misalignment: A mechanistic review.

The rising prevalence of obesity is a major international concern and is associated with a substantial burden of disease. Disrupted circadian behaviours, including late and extended eating patterns, are identified as risk factors for obesity. The circadian rhythm synchronises metabolic functions between and within tissues, optimising physiology to integrate with environmental and behavioural cycles. Cellular circadian rhythms also separate poorly compatible processes and enable adaptive integration of energy metabolism with autophagy. The timing of nutritional input is a key and easily controllable variable that influences circadian function. Misalignment of nutritional input with the centrally generated circadian rhythm may dampen and disrupt circadian metabolic function. This review seeks to provide a mechanistic overview of nutritional circadian entrainment and its downstream metabolic effects. The aims are: to characterise the key cellular and physiological mechanisms involved in the nutritional entrainment of circadian rhythms; and to explore the perturbation of these pathways by misaligned nutritional inputs, with relevance to obesity-associated dysmetabolism. A systematic two-tranche search strategy was employed. Searches were conducted within PubMed between March and December 2020. Included studies were formally evaluated for quality. Evidence was extracted and coded into key themes. 142 records were screened and 50 accepted. The evidence analysed was moderate-to-high quality and enabled the detailed characterisation of cellular pathways involved in nutritional circadian entrainment. Results indicated that diverse nutritional input pathways converge upon key nutrient/redox sensors and nutritionally sensitive core clock genes, which integrate with circadian metabolic pathways, allowing bidirectional communication between circadian clock function and metabolism. Versus alignment, nutritional misalignment was causally associated with dampening and alteration of core clock rhythms, between-tissue rhythmic decoupling, dysmetabolism, and obesity. Signalling through key circadian nodes, such as NAD+/SIRT, was indicated to have importance in these metabolic changes. Misaligned nutritional inputs were associated with altered core circadian temporal dynamics of metabolism and autophagy, and different time division between insulin-sensitive and insulin-resistant metabolic states. Time-restricted feeding protocols aligned with the natural circadian rhythm (light-dark cycle) relatively strengthened circadian oscillatory patterns and protected against diet-induced obesity. This review suggests potential value in further investigating circadian-normalising nutritional interventions for obesity, such as circadian-aligned time-restricted feeding.