Modulation of circadian clocks by nutrients and food factors

Daily activity rhythms that are dominated by internal clocks are called circadian rhythms. A central clock is located in the suprachiasmatic nucleus of the hypothalamus, and peripheral clocks are located in most mammalian peripheral cells. The central clock is entrained by light/dark cycles, whereas peripheral clocks are entrained by feeding cycles. The effects of nutrients on the central and peripheral clocks have been investigated during the past decade and much interaction between them has come to light. For example, a high-fat diet prolongs the period of circadian behavior, a ketogenic diet advances the onset of locomotor activity rhythms, and a high-salt diet advances the phase of peripheral molecular clocks. Moreover, some food factors such as caffeine, nobiletin, and resveratrol, alter molecular and/or behavioral circadian rhythms. Here, we review nutrients and food factors that modulate mammalian circadian clocks from the cellular to the behavioral level.     

To be or not to be rhythmic? A review of studies on organisms inhabiting constant environments

Abstract

Circadian clocks are endogenous time keeping mechanisms that drive near 24-h behavioural, physiological and metabolic rhythms in organisms. It is thought that organisms possess circadian clocks to facilitate coordination of essential biological events to the external day and night (extrinsic advantage) so as to enhance Darwinian fitness. However, on Earth, there are a number of habitats that are not subject to such robust daily cycling of geo-physical factors. Do organisms living under such conditions exhibit rhythmic behaviours that are driven by endogenous circadian clocks? We attempt to critically survey studies of rhythms (or the lack of them) in organisms living in a range of constant environments. Many such organisms do show rhythms in behaviour and/or physiological variables. We suggest that such presence of rhythms may be indicative of an underlying clock that facilitates, (a) internal synchrony among rhythms, and (b) temporal partitioning of incompatible cellular processes (intrinsic advantage). We then highlight reasons that limit our interpretations about the presence (or absence) of clocks in such organisms living under constant conditions, and suggest possible methods to conclusively test whether or not rhythms in these organisms are driven by endogenous circadian clocks with the hope that it may enhance our understanding of circadian clocks in organisms under constant environments.     

Insect circadian clocks: is it all in their heads?

Circadian rhythms are ubiquitous in living organisms, synchronizing life functions at the biochemical, physiological, and behavioral levels. The rhythm-generating mechanisms, collectively known as circadian clocks, are not fully understood in any organism. Research in the fruit fly Drosophila has led to the identification of several clock genes that are involved in the function of the brain-centered clock, which controls behavioral rhythms of adult flies. With the use of clock genes as markers, putative circadian clocks were mapped in the fly peripheral organs and shown to be independent from clocks located in the brain. A homologue of fruit fly period gene has been identified in moths and other insects, allowing investigations of this gene's role in known insect rhythms. This approach may increase our understanding of how circadian clocks are organized into the circadian system that orchestrates temporal integration of life processess in insects.     

Cyclic presence and absence of conspecifics alters circadian clock phase but does not entrain the locomotor activity rhythm of the fruit fly Drosophila melanogaster

Circadian clocks use a wide range of environmental cues, including cycles of light, temperature, food, and social interactions, to fine-tune rhythms in behavior and physiology. Although social cues have been shown to influence circadian clocks of a variety of organisms including the fruit fly Drosophila melanogaster, their mechanism of action is still unclear. Here, the authors report the results of their study aimed at investigating if daily cycles of presence and absence (PA) of conspecific male visitors are able to entrain the circadian locomotor activity rhythm of male hosts living under constant darkness (DD). The results suggest that PA cycles may not be able to entrain circadian locomotor activity rhythms of Drosophila. The outcome does not change when male hosts are presented with female visitors, suggesting that PA cycles of either sex may not be effective in bringing about stable entrainment of circadian clocks in D. melanogaster. However, in hosts whose clock phase has already been set by light/dark (LD) cycles, daily PA cycles of visitors can cause measurable change in the phase of subsequent free-running rhythms, provided that their circadian clocks are labile. Thus, the findings of this study suggest that D. melanogaster males may not be using cyclic social cues as their primary zeitgeber (time cue) for entrainment of circadian clocks, although social cues are capable of altering the phase of their circadian rhythms.     

Peripheral circadian rhythms and their regulatory mechanism in insects and some other arthropods: a review

Many physiological functions of insects show a rhythmic change to adapt to daily environmental cycles. These rhythms are controlled by a multi-clock system. A principal clock located in the brain usually organizes the overall behavioral rhythms, so that it is called the "central clock". However, the rhythms observed in a variety of peripheral tissues are often driven by clocks that reside in those tissues. Such autonomous rhythms can be found in sensory organs, digestive and reproductive systems. Using Drosophila melanogaster as a model organism, researchers have revealed that the peripheral clocks are self-sustained oscillators with a molecular machinery slightly different from that of the central clock. However, individual clocks normally run in harmony with each other to keep a coordinated temporal structure within an animal. How can this be achieved? What is the molecular mechanism underlying the oscillation? Also how are the peripheral clocks entrained by light-dark cycles? There are still many questions remaining in this research field. In the last several years, molecular techniques have become available in non-model insects so that the molecular oscillatory mechanisms are comparatively investigated among different insects, which give us more hints to understand the essential regulatory mechanism of the multi-oscillatory system across insects and other arthropods. Here we review current knowledge on arthropod's peripheral clocks and discuss their physiological roles and molecular mechanisms.     

Diurnal and annual rhythms in trees

Trees, perennial phanerophytes, display a rich variety of rhythmic phenomena. These are either due to exclusive environmental entrainment or due to the functioning of endogenous oscillators independent of the environment. Both types of rhythms are covered in this review. Purely environment controlled rhythms may be considered as a prelude to endogenous rhythms. Environment controlled rhythms discussed are (i) the diurnal rhythms of nyctinastic and heliotropic leaf movements and oscillatory phenomena of photosynthesis, such as the midday depression and Crassulacean acid metabolism (CAM), and (ii) the annual rhythms of annual growth ring formation, autumnal leaf senescence, over wintering mechanisms and flowering. Among the diurnal rhythms, nyctinastic movements and CAM are also free-running endogenous rhythms showing the operation of circadian clocks in trees. In leaf senescence, over wintering, and flowering control, photoperiod sensing is involved which suggests the participation of endogenous clocks. A question asked is if diurnal and annual rhythms are mechanistically correlated. Evidently, phenological phenomena based on photoperiodism (as dependent on measurement of night length) are co-ordinately regulated by the phytochrome system and the circadian clocks and many aspects of annual developments and over wintering are linked to photoperiodism. The existence in trees of circadian clock genes as known to be anchored in the genome of A. thaliana can be assessed by attempts of alignment with the sequenced genome of Populus or by isolating cDNA clones from trees to check them against the genome of A. thaliana. At extreme latitudes near the equator and north of the polar circle trees also display photoperiod-independent phenological phenomena. In the polar region, total irradiance of red and far red light could possibly be involved and the signalling pathway then involves phytochrome, and thus, may still be similar to that of photoperiodism. At the equator, total daily light irradiance received or sensing the dynamics of daily changes in solar irradiance are essential and it remains enigmatic whether signalling cascades are either attached to the circadian clocks in a still unknown way or totally independent of circadian clocks.     

Evolution of circadian rhythms in Drosophila melanogaster populations reared in constant light and dark regimes for over 330 generations

Organisms are believed to have evolved circadian clocks as adaptations to deal with cyclic environmental changes, and therefore it has been hypothesized that evolution in constant environments would lead to regression of such clocks. However, previous studies have yielded mixed results, and evolution of circadian clocks under constant conditions has remained an unsettled topic of debate in circadian biology. In continuation of our previous studies, which reported persistence of circadian rhythms in Drosophila melanogaster populations evolving under constant light, here we intended to examine whether circadian clocks and the associated properties evolve differently under constant light and constant darkness. In this regard, we assayed activity-rest, adult emergence and oviposition rhythms of D. melanogaster populations which have been maintained for over 19 years (~330 generations) under three different light regimes – constant light (LL), light–dark cycles of 12:12 h (LD) and constant darkness (DD). We observed that while circadian rhythms in all the three behaviors persist in both LL and DD stocks with no differences in circadian period, they differed in certain aspects of the entrained rhythms when compared to controls reared in rhythmic environment (LD). Interestingly, we also observed that DD stocks have evolved significantly higher robustness or power of free-running activity-rest and adult emergence rhythms compared to LL stocks. Thus, our study, in addition to corroborating previous results of circadian clock evolution in constant light, also highlights that, contrary to the expected regression of circadian clocks, rearing in constant darkness leads to the evolution of more robust circadian clocks which may be attributed to an intrinsic adaptive advantage of circadian clocks and/or pleiotropic functions of clock genes in other traits.     

Monitoring circadian rhythms of individual cells in plants

The circadian clock is an endogenous timing system based on the self-sustained oscillation in individual cells. These cellular circadian clocks compose a multicellular circadian system working at respective levels of tissue, organ, plant body. However, how numerous cellular clocks are coordinated within a plant has been unclear. There was little information about behavior of circadian clocks at a single-cell level due to the difficulties in monitoring circadian rhythms of individual cells in an intact plant. We developed a single-cell bioluminescence imaging system using duckweed as the plant material and succeeded in observing behavior of cellular clocks in intact plants for over a week. This imaging technique quantitatively revealed heterogeneous and independent manners of cellular clock behaviors. Furthermore, these quantitative analyses uncovered the local synchronization of cellular circadian rhythms that implied phase-attractive interactions between cellular clocks. The cell-to-cell interaction looked to be too weak to coordinate cellular clocks against their heterogeneity under constant conditions. On the other hand, under light–dark conditions, the heterogeneity of cellular clocks seemed to be corrected by cell-to-cell interactions so that cellular clocks showed a clear spatial pattern of phases at a whole plant level. Thus, it was suggested that the interactions between cellular clocks was an adaptive trait working under day–night cycles to coordinate cellular clocks in a plant body. These findings provide a novel perspective for understanding spatio-temporal architectures in the plant circadian system.     

Circadian rhythms from multiple oscillators: lessons from diverse organisms

The organization of biological activities into daily cycles is universal in organisms as diverse as cyanobacteria, fungi, algae, plants, flies, birds and man. Comparisons of circadian clocks in unicellular and multicellular organisms using molecular genetics and genomics have provided new insights into the mechanisms and complexity of clock systems. Whereas unicellular organisms require stand-alone clocks that can generate 24-hour rhythms for diverse processes, organisms with differentiated tissues can partition clock function to generate and coordinate different rhythms. In both cases, the temporal coordination of a multi-oscillator system is essential for producing robust circadian rhythms of gene expression and biological activity.     

Activation of Phospholipase C Mimics the Phase Shifting Effects of Light on Melatonin Rhythms in Retinal Photoreceptors

Many aspects of retinal photoreceptor function and physiology are regulated by the circadian clocks in these cells. It is well established that light is the primary stimulus that entrains these clocks; yet, the biochemical cascade(s) mediating light’s effects on these clocks remains unknown. This deficiency represents a significant gap in our fundamental understanding of photoreceptor signaling cascades and their functions. In this study, we utilized re-aggregated spheroid cultures prepared from embryonic chick retina to determine if activation of phospholipase C in photoreceptors in the absence of light can phase shift the melatonin secretion rhythms of these cells in a manner similar to that induced by light. We show that spheroid cultures rhythmically secrete melatonin and that these melatonin rhythms can be dynamically phase shifted by exposing the cultures to an appropriately timed light pulse. Importantly, we show that activation of phospholipase C using m-3M3FBS in the absence of light induces a phase delay in photoreceptor melatonin rhythms that mirrors that induced by light. The implication of this finding is that the light signaling cascade that entrains photoreceptor melatonin rhythms involves activation of phospholipase C.     

The current state and problems of circadian clock studies in cyanobacteria

Circadian rhythms have been observed in innumerable physiological processes in most of organisms. Recent molecular and genetic studies on circadian clocks in many organisms have identified and characterized several molecular regulatory factors that contribute to generation of such rhythms. The cyanobacterium is the simplest organism known to harbor circadian clocks, and it has become one of most successful model organisms for circadian biology. In this review, we will briefly summarize physiological observations and consideration of circadian rhythms in cyanobacteria, molecular genetics of the clock using Synechococcus, and current knowledge of the input and output pathways that support the cellular circadian system. Finally, we will document some current problems in the studies on the cyanobacterial circadian clock.     

Circadiane Uhren und Energiemetabolismus

Chrononutrition – circadian clocks and energy metabolism Genetically encoded endogenous clocks regulate 24‐hour rhythms of physiology and behavior. A central pacemaker residing in the suprachiasmatic nucleus synchronizes peripheral clocks found in all tissues with each other and with the external day‐night cycle. One function of circadian clocks is the regulation of energy metabolism via rhythmic activation of tissue‐specific clock‐controlled genes. In the liver, genes involved in glucose and lipid metabolism are regulated in this fashion, while in adipocytes, fatty acid release and adipokine secretion are controlled by the circadian clock. Disruption of circadian rhythms as seen, for example, in shift workers promotes the development of metabolic disorders such as obesity and type‐2 diabetes.     

Rhythms of locomotion expressed by Limulus polyphemus, the American horseshoe crab: II. Relationship to circadian rhythms of visual sensitivity

In the laboratory, horseshoe crabs express a circadian rhythm of visual sensitivity as well as daily and circatidal rhythms of locomotion. The major goal of this investigation was to determine whether the circadian clock underlying changes in visual sensitivity also modulates locomotion. To address this question, we developed a method for simultaneously recording changes in visual sensitivity and locomotion. Although every animal (24) expressed consistent circadian rhythms of visual sensitivity, rhythms of locomotion were more variable: 44% expressed a tidal rhythm, 28% were most active at night, and the rest lacked statistically significant rhythms. When exposed to artificial tides, 8 of 16 animals expressed circatidal rhythms of locomotion that continued after tidal cycles were stopped. However, rhythms of visual sensitivity remained stable and showed no tendency to be influenced by the imposed tides or locomotor activity. These results indicate that horseshoe crabs possess at least two biological clocks: one circadian clock primarily used for modulating visual sensitivity, and one or more clocks that control patterns of locomotion. This arrangement allows horseshoe crabs to see quite well while mating during both daytime and nighttime high tides.     

Light exposure mediates circadian rhythms of rhizosphere microbial communities

Microbial community circadian rhythms have a broad influence on host health and even though light-induced environmental fluctuations could regulate microbial communities, the contribution of light to the circadian rhythms of rhizosphere microbial communities has received little attention. To address this gap, we monitored diel changes in the microbial communities in rice (Oryza sativa L.) rhizosphere soil under light–dark and constant dark regimes, identifying microbes with circadian rhythms caused by light exposure and microbial circadian clocks, respectively. While rhizosphere microbial communities displayed circadian rhythms under light–dark and constant dark regimes, taxa possessing circadian rhythms under the two conditions were dissimilar. Light exposure concealed microbial circadian clocks as a regulatory driver, leading to fewer ecological niches in light versus dark communities. These findings disentangle regulation mechanisms for circadian rhythms in the rice rhizosphere microbial communities and highlight the role of light-induced regulation of rhizosphere microbial communities.Subject terms: Microbial ecology, Community ecology     

Circadian orchestration of developmental hormones in the insect, Rhodnius prolixus

This review presents a new perspective on the circadian regulation and functions of insect developmental hormones. In Rhodnius prolixus (Hemiptera), the brain neuropeptide prothoracicotropic hormone (PTTH) is released with a circadian rhythm that is controlled by paired photosensitive clocks in the brain. These clocks comprise the dorsal and lateral PER/TIM clock neurons known to regulate behavioral rhythms in Drosophila. Axons of PTTH and clock cells make close contact. Photosensitive PER/TIM clocks also reside in the paired prothoracic glands (PGs), which generate rhythmic synthesis and release of the ecdysteroid molting hormones. The PG clocks are entrained by both light and PTTH. These four clocks are coupled together by both nerves and hormones into a timing system whose primary regulated output is the circadian rhythm of ecdysteroids in the hemolymph. This complex timing system appears necessary to ensure circadian organization of the gene expression that is induced in target cells by ecdysteroids via circadian cycling of the nuclear ecdysteroid receptor (EcR). This multioscillator system serves to transduce 'the day outside' into endocrine rhythms that orchestrate 'the day inside'. It has many functional similarities with vertebrate circadian systems.     

Global orchestration of gene expression by the biological clock of cyanobacteria

Prokaryotic cyanobacteria express robust circadian (daily) rhythms under the control of a central clock. Recent studies shed light on the mechanisms governing circadian rhythms in cyanobacteria and highlight key differences between prokaryotic and eukaryotic clocks.     

Behavioral analysis of circadian rhythms: Entraining the circadian clock and determining the food-entrainable oscillator mechanism

Sleep and Biological Rhythms - Circadian rhythms are oscillations in behavior and physiological functions that are regulated by internal biological clocks. In mammals, the circadian rhythms can be...