Feeding Rhythms Research Articles

Apple polyphenol extract modulates bile acid metabolism and gut microbiota by regulating the circadian rhythms in daytime-restricted high fat diet feeding C57BL/6 male mice.

The homeostasis of circadian clock linked to bile acid (BA) metabolism and gut microbiota has profound benefits in maintaining the health status of the host. The aim of this study was to investigate the prevention and regulation of apple polyphenol extract (APE) on BA metabolism and gut microbiota by means of modulation of circadian rhythms in mice. Eighty male C57BL/6 mice were randomized into four groups: 24-hour ad libitum standard chow group (AC), ad libitum HFD group (AF), restricted 12 h daytime HFD feeding group (DF), and daytime HFD feeding with APE treatment group (DP). Five weeks later, the mice were sacrificed at 6 h intervals over a 24 h period. The results showed that APE decreased body weight and induced daily rhythms of Cry1 and Rorα in the suprachiasmatic nucleus (SCN) and Clock, Cry1 and Cry2 in the ileum in daytime HFD mice. APE significantly increased the expression of hepatic FXR at ZT0 and BSEP at ZT12 and inhibited the expression of ileac FXR at ZT12, reduced levels of fecal TBAs, secondary BAs, and unconjugated BAs at ZT0. Meanwhile, APE regulated the diversity and composition of the gut microbiota, and increased the abundance of probiotics. Therefore, our work revealed that APE as a clock-regulating natural compound could modulate BA metabolism and gut microbiota and protect against circadian disruption in a clock-dependent manner.

Sleep/waketime preference and delayed diurnal eating rhythms are associated through light exposure timing and modified by sleep efficiency

Delayed eating rhythms, relative to the sleep/wake period, commonly manifest as a lack of hunger in the morning (morning anorexia) and elevated hunger in the late evening (evening hyperphagia). These intake patterns are associated with adverse mental and physical health outcomes. We aimed to evaluate whether the timing of light exposure, an important environmental signal for circadian synchronization, explains the link between sleep/waketime preferences and delayed diurnal appetite. We also aimed to test whether disruptions in sleep quality, reflecting suboptimal circadian synchronization, identify individuals for whom sleep/waketime preference is associated with delayed diurnal appetite. Participants (N = 150) completed a measure of their sleep/waketime preferences and wore a device to capture their sleep efficiency and naturalistic light exposure for 48 consecutive hours. The timing of light exposure mediated the link between sleep/waketime preferences and evening hyperphagia, but not morning anorexia, such that a later peak in light exposure mitigated some of the risk for evening hyperphagia that was associated with later sleep/waketime preferences. Sleep efficiency moderated the association between sleep/waketime preference and morning anorexia, but not evening hyperphagia. Earlier sleep/waketime preference was associated with less morning anorexia among individuals with high sleep efficiency, but morning anorexia was consistently elevated among individuals with poor sleep efficiency. These results on the relation between sleep/waketime preference and two aspects of delayed diurnal appetite suggest that morning anorexia depends on sleep efficiency and evening hyperphagia may be influenced by the timing of daily light exposure. Future research should assess over longer periods, covering weekdays and weekends, and incorporate momentary reports of meals/snacks and appetite.

Seasonal effects on locomotor and feeding rhythms in indoor cats

Different synchronizers can modify daily rhythms during an annual cycle. Nevertheless, the fluctuation of these external factors is often ignored in studies on cat locomotor activity and feeding rhythms, thereby focusing on one single season. To fill this gap, the activity and feeding rhythms of six cats living in a research cattery, receiving natural daylight, were monitored during 3 weeks for each season. Although under minimal influence of seasonal fluctuations in ambient temperature and humidity, the cats showed maxima in daily covered distance during spring and autumn, and minima during winter. The activity and feeding rhythms followed 24-hour periodicity during all seasons and bimodality was detected, with decreased covered distance and food intake around midnight and midday. These daily rhythm troughs were robust and stable across seasons, whereas the inter-seasonal differences in activity level resided in the timing of daily peaks. However, the daily eating pattern was less affected by seasonal variations. Human interactions systematically enhanced locomotor activity and food consumption at the same time for each season, whereas spontaneous peaks of feeding and activity rose during the twilight times according to the season, confirming the crepuscular nature of the species. Human presence and attention seem responsible for more diurnal patterns in the studied cats. This study demonstrates that natural seasonal daylight fluctuations modulate the locomotor and feeding rhythms of indoor cats.

Effects of Night Illumination on Behavior, Body Mass and Learning in Male Zebra Finches

An increase in artificial night lighting has blurred the boundaries of day and night and transformed the natural day-night environment with alteration in the temporal niche of the animals. Male zebra finches were exposed to a dim light at night (dLAN) protocol (Light: dLAN, 12L = 200 lux: 12dLAN = 5 lux) with controls on darkness at night (Light: dark, 12L = 200 lux: 12D = 0 lux) for six weeks. We assayed sleep-wake, daily behaviors, mood, and cognition, as well as changes in physiological parameters. Dim light at night increased sleep frequency, delayed sleep onset, advanced awakening latency, and caused a reduction in total sleep duration. dLAN birds did not associate (physical association) with novel object and birds spent significantly lesser time on perch with novel object as compared to LD. In colour learning task, night illuminated birds took more time to learn and made more error, compared to LD. dLAN significantly altered the 24-h daily behavioral rhythm (amplitude and acrophase) of feeding, drinking, preening, and perch-hopping behavior. In particular, birds extended their feeding hours in the nighttime under dLAN, with no difference in total food intake. Birds under dLAN increased fattening and hence significantly increased body mass. Our results show that dim light at night altered feeding rhythm, caused decrease in sleep behavior, and negatively affected learning and memory performance in male zebra finches.

Time to eat reveals the hierarchy of peripheral clocks.

Meal timing resets trillions of cellular circadian clocks in the body. Recent advances in multiomics demonstrate that clocks in peripheral tissues are differentially reset by feeding rhythm, and modulated by the central clock and the liver clock. This highlights the essential roles of tissue-specific regulation and intercellular signaling in clock synchronization.

Astrocyte Gliotransmission in the Regulation of Systemic Metabolism.

Normal brain function highly relies on the appropriate functioning of astrocytes. These glial cells are strategically situated between blood vessels and neurons, provide significant substrate support to neuronal demand, and are sensitive to neuronal activity and energy-related molecules. Astrocytes respond to many metabolic conditions and regulate a wide array of physiological processes, including cerebral vascular remodeling, glucose sensing, feeding, and circadian rhythms for the control of systemic metabolism and behavior-related responses. This regulation ultimately elicits counterregulatory mechanisms in order to couple whole-body energy availability with brain function. Therefore, understanding the role of astrocyte crosstalk with neighboring cells via the release of molecules, e.g., gliotransmitters, into the parenchyma in response to metabolic and neuronal cues is of fundamental relevance to elucidate the distinct roles of these glial cells in the neuroendocrine control of metabolism. Here, we review the mechanisms underlying astrocyte-released gliotransmitters that have been reported to be crucial for maintaining homeostatic regulation of systemic metabolism.

Factors involved in enhancing host susceptibility towards aphid clonal propagation on leaf foliage of Arabidopsis

The present study identified factors that enhanced host susceptibility towards Myzus persicae’s clonal proliferation in the model plant, Arabidopsis thaliana. A particular aphid inoculum, i.e. five aphids release per plant among three inoculums (1, 5 and 10 aphids per plant) showed enhanced susceptibility towards aphid clonal propagation in 21-day-old Arabidopsis leaf foliage. Five aphid number was common among the 28, 35, 42, 49-day-old Arabidopsis leaf foliage except 42-day-old Arabidopsis. Prior aphid herbivory enhan­ced host susceptibility in Arabidopsis. The aphid ino­culum at 6 am showed enhanced host susceptibility in comparison to 12 noon and 6 pm. The enhanced susceptibility on leaf foliage was realized in the presence of flower stalk. Aphid preferred to proliferate significantly on the flower stalk as compared to leaf foliage. Within leaf, aphid colonized more in mid-rib region as compared to minor vein area in the mature leaf. ProPAD4 :: GUS and ProADF3 :: GUS showed poor expression in mid-rib region in aphid-challenged leaf foliage. The aphid feeding based primed vascular sap showed degraded peptide bond, a possible reason for favouring enhanced aphid clonal proliferation in the primed Arabidopsis leaf foliage. Results showed that the enhancing of host susceptibility in Arabidopsis to Myzus persicae is influenced by quorum number of aphid’s inoculum, prior aphid feeding and circadian rhythms. Differential spatial resistance within whole plant and within leaf was also recorded. The enhanced host susceptibility was also correlated with microbiota enrichment in aphid-herbivore leaf vasculature sap as well as aphid body including aphid apical part containing salivary gland

DFRAME: A Video Recording-Based Analytical Method for Studying Feeding Rhythm in Drosophila

Animals, from insects to humans, exhibit obvious diurnal rhythmicity of feeding behavior. Serving as a genetic animal model, Drosophila has been reported to display feeding rhythms; however, related investigations are limited due to the lack of suitable and practical methods. Here, we present a video recording-based analytical method, namely, Drosophila Feeding Rhythm Analysis Method (dFRAME). Using our newly developed computer program, FlyFeeding, we extracted the movement track of individual flies and characterized their food-approaching behavior. To distinguish feeding and no-feeding events, we utilized high-magnification video recording to optimize our method by setting cut-off thresholds to eliminate the interference of no-feeding events. Furthermore, we verified that this method is applicable to both female and male flies and for all periods of the day. Using this method, we analyzed long-term feeding status of wild-type and period mutant flies. The results recaptured previously reported feeding rhythms and revealed detailed profiles of feeding patterns in these flies under either light/dark cycles or constant dark environments. Together, our dFRAME method enables a long-term, stable, reliable, and subtle analysis of feeding behavior in Drosophila. High-throughput studies in this powerful genetic animal model will gain great insights into the molecular and neural mechanisms of feeding rhythms.

The Discovery of Circadian Rhythm of Feeding Time on Digestive Enzymes Activity and Their Gene Expression in Sinonovacula constricta Within a Light/Dark Cycle

The circadian rhythm has a great impact on the growth, metabolism and development of animals, but little is known about the circadian rhythm of marine bivalves. Understanding of the feeding rhythm is of great significance to increase the yield of razor clam Sinonovacula constricta, an economically important bivalve mollusk. The aim of this experiment was to study the effects of circadian rhythm of feeding time on digestive enzymes activities and their gene expression in S. constricta within a light (ZT8-ZT20)/dark (ZT20-ZT8) cycle. The present results showed that circadian rhythm of feeding rate (FR) was highly associated with digestive enzyme activities and relative expression of their genes. The highest values of FR were basically observed in the night from ZT0-ZT2 and ZT6-ZT8, which were significantly higher than those values in the daytime from ZT12-ZT14 and ZT18-ZT20 (P < 0.05). The digestive enzymes activities displayed the highest values at ZT2 and ZT8, and the lowest at ZT14 and ZT20. Among them, cellulase and pepsin were found to have significantly different activities (P < 0.05), rather than amylase and lipase. Notably, the relative expression of digestive enzyme genes shared the similar pattern with the activities of digestive enzymes. The highest values of relative gene expression of amylase (AMY), lipase (LIP), cellulase (CEL), and pepsin (PEP) were found at ZT2 and ZT8 in the night, while the lowest values were found at ZT14 during the day. It is therefore suggested that the biological clock may regulate the process from feeding to digestion. Furthermore, it might be better to feed at night to reduce cultivating cost and increase economic benefits in the farming industry of S. constricta.

Feeding Rhythm-Induced Hypothalamic Agouti-Related Protein Elevation via Glucocorticoids Leads to Insulin Resistance in Skeletal Muscle.

Circadian phase shifts in peripheral clocks induced by changes in feeding rhythm often result in insulin resistance. However, whether the hypothalamic control system for energy metabolism is involved in the feeding rhythm-related development of insulin resistance is unknown. Here, we show the physiological significance and mechanism of the involvement of the agouti-related protein (AgRP) in evening feeding-associated alterations in insulin sensitivity. Evening feeding during the active dark period increased hypothalamic AgRP expression and skeletal muscle insulin resistance in mice. Inhibiting AgRP expression by administering an antisense oligo or a glucocorticoid receptor antagonist mitigated these effects. AgRP-producing neuron-specific glucocorticoid receptor-knockout (AgRP-GR-KO) mice had normal skeletal muscle insulin sensitivity even under evening feeding schedules. Hepatic vagotomy enhanced AgRP expression in the hypothalamus even during ad-lib feeding in wild-type mice but not in AgRP-GR-KO mice. The findings of this study indicate that feeding in the late active period may affect hypothalamic AgRP expression via glucocorticoids and induce skeletal muscle insulin resistance.

Central and Peripheral Clock Control of Circadian Feeding Rhythms.

Many behaviors exhibit ~24-h oscillations under control of an endogenous circadian timing system that tracks time of day via a molecular circadian clock. In the fruit fly, Drosophila melanogaster, most circadian research has focused on the generation of locomotor activity rhythms, but a fundamental question is how the circadian clock orchestrates multiple distinct behavioral outputs. Here, we have investigated the cells and circuits mediating circadian control of feeding behavior. Using an array of genetic tools, we show that, as is the case for locomotor activity rhythms, the presence of feeding rhythms requires molecular clock function in the ventrolateral clock neurons of the central brain. We further demonstrate that the speed of molecular clock oscillations in these neurons dictates the free-running period length of feeding rhythms. In contrast to the effects observed with central clock cell manipulations, we show that genetic abrogation of the molecular clock in the fat body, a peripheral metabolic tissue, is without effect on feeding behavior. Interestingly, we find that molecular clocks in the brain and fat body of control flies gradually grow out of phase with one another under free-running conditions, likely due to a long endogenous period of the fat body clock. Under these conditions, the period of feeding rhythms tracks with molecular oscillations in central brain clock cells, consistent with a primary role of the brain clock in dictating the timing of feeding behavior. Finally, despite a lack of effect of fat body selective manipulations, we find that flies with simultaneous disruption of molecular clocks in multiple peripheral tissues (but with intact central clocks) exhibit decreased feeding rhythm strength and reduced overall food intake. We conclude that both central and peripheral clocks contribute to the regulation of feeding rhythms, with a particularly dominant, pacemaker role for specific populations of central brain clock cells.

Human trampling decreases surface activity and disturbs behavioral rhythm of an endangered intertidal crab

Human recreational visits to tidal flats increase trampling pressure, which has a significant impact on the coastal benthic ecosystem. The fiddler crab Austruca lactea, which inhabits the upper intertidal region, is endangered in temperate regions such as Japan and South Korea. The vulnerability of their habitat to human activities along with their limited summer reproduction period may have contributed to the decrease in fiddler crab populations in these regions. We conducted experiments to elucidate the effects of trampling on the surface activities and courtship behaviors of A. lactea, which represent ecological indicators for tidal flat ecosystems. During the 46-day trampling period, we observed the number of active crabs on the surface of the tidal flat under three different trampling intensities (heavy trampling = 60 steps/m2; moderate trampling = 20 steps/m2; and no trampling). The density of individuals of both sexes active on the surface and that of courting males significantly decreased under both heavy and moderate trampling intensities. In addition, the feeding and courtship rhythms of male A. lactea collapsed under continuous trampling events. We monitored the site once per week, and surface activity did not recover fully until the sixth week after the trampling period. Our results demonstrated that trampling on the tidal flat disrupted the intensity and timing of crab surface behavior and male reproductive surface behavior, and thus may, ultimately, have an impact on the population dynamics of A. lactea.

The Effect of Severe Intraventricular Hemorrhage on the Biorhythms of Feeding in Premature Infants.

Background: Suck-swallow rhythmicity and the integration of breathing into infant feeding are developmentally regulated. Neurological injury and breathing abnormalities can both impact feeding in preterm infants.Objective: To determine the effects of neurologic injury independent of effects of disordered breathing on feeding biorhythms in premature infants.Methods: Low-risk preterm infants (LRP), infants with Grade 3–4 Intraventricular Hemorrhage (IVH), those with bronchopulmonary dysplasia (BPD), and those with both BPD and IVH (BPD+IVH) were identified. Forty-seven infants, 32–42 weeks Postmenstrual Age (PMA) were evaluated on one or more occasions (131 studies). Of these, 39 infants (81 studies) were performed at >35 weeks PMA. Coefficient of variation (COV) (=standard deviation of the inter-event (e.g., suck-suck, swallow-breath, etc.) interval divided by the mean of the interval) was used to quantify rhythmic stability.Results: To adjust for PMA, only those infants >35–42 weeks were compared. Suck-suck COV was significantly lower (more rhythmically stable) in the LRP group [COV = 0.274 ± 0.051 (S.D.)] compared to all other groups (BPD = 0.325 ± 0.066; IVH = 0.342 ± 0.072; BPD + IVH = 0.314 ± 0.069; all p < 0.05). Similarly, suck-swallow COV was significantly lower in LRP babies (0.360 ± 0.066) compared to the BPD group (0.475 ± 0.113) and the IVH cohort (0.428 ± 0.075) (p < 0.05). The BPD+IVH group (0.424 ± 0.109), while higher, was not quite statistically significant.Conclusions: Severe IVH negatively impacts suck-suck and suck-swallow rhythms. The independent effect of neurological injury in the form of IVH on feeding rhythms suggests that quantitative analysis of feeding may reflect and predict neurological sequelae.

The microbiota coordinates diurnal rhythms in innate immunity with the circadian clock

Environmental light cycles entrain circadian feeding behaviors in animals that produce rhythms in exposure to foodborne bacteria. Here, we show that the intestinal microbiota generates diurnal rhythms in innate immunity that synchronize with feeding rhythms to anticipate microbial exposure. Rhythmic expression of antimicrobial proteins was driven by daily rhythms in epithelial attachment by segmented filamentous bacteria (SFB), members of the mouse intestinal microbiota. Rhythmic SFB attachment was driven by the circadian clock through control of feeding rhythms. Mechanistically, rhythmic SFB attachment activated an immunological circuit involving group 3 innate lymphoid cells. This circuit triggered oscillations in epithelial STAT3 expression and activation that produced rhythmic antimicrobial protein expression and caused resistance to Salmonella Typhimurium infection to vary across the day-night cycle. Thus, host feeding rhythms synchronize with the microbiota to promote rhythms in intestinal innate immunity that anticipate exogenous microbial exposure.

Alteration of gut microbiota and metabolomics in critically ill patients by sequential feeding: A pilot study.

Sequential feeding (SF) is a new feeding mode for critically ill patients that involves a combination of continuous feeding (CF) in the beginning, rhythmic feeding in the second stage, and oral feeding in the last stage. In this study, we investigated the influence of SF on gut microbiota and metabolomics in critically ill patients. Stool specimens from 20 patients (10 patients with the SF group, 10 patients with the CF group) were collected for full-length 16S ribosomal RNA gene sequencing and untargeted metabolomics analysis. The proportion of patients with low bacterial diversity (Shannon index < 4) in the SF group was much lower than that in the CF group, but there was no significant difference in the proportions (20% vs 50%, P = .350). The abundances of Actinobacteria/Actinobacteria (at the phylum and class levels), Pseudomonadaceae/Pseudomonas (at the family and genus levels), and Fusobacteria/Fusobacteriaceae/Fusobacteriales/Fusobacteria/Fusobacterium (at the phylum, class, order, family, and genus levels) were all higher in the SF group than in the CF group. Actinobacteria/Actinobacteria (at the phylum and class levels) were the most influential of these gut flora. Retinoic acid and leucine were upregulated in the SF group and were respectively responsible for the intestinal immune network for immunoglobulin A production and the mammalian target of rapamycin signaling pathway in the enriched pathways according to the Kyoto Encyclopedia of Genes and Genomes database classification. SF could alter gut microbiota and metabolomics in critically ill patients. Because of the small sample size, further study is required.

Machinery feeding development for sustainable aquaculture: Self-feeding system

Demand feeder is slightly different with an automatic feeder, it is altered to the appetite of fish because they can prefer which time they activate the feeder, also it triggered to produce a good growth performance and decrease the feed waste. Alternatively, some studies have been carried out for new method of automatic feeding system. Self-feeding system or previously familiar with the name of demand feeding system, is a system based on the learning ability of fish to activate the feeder and utilizing a feeding rhythm that may be controlled by the biological clock. At the past two decades, the development of self-feeding system is growing rapidly, from database, twenty eight studies with the most relevant data have been collected. The peak of paper published was in year 2000 with the most popular fish species was European sea bass (Dicentrarchus labrax, L.).

Diel Feeding Rhythm and Grazing Selectivity of Small-Sized Copepods in a Subtropical Embayment, the Northern South China Sea

Small marine copepods are key components of the pelagic food webs in Chinese coastal waters, but very few studies have addressed their trophodynamics, with even fewer studies addressing their diel feeding rhythms. In this study, the diel feeding rhythm and grazing selectivity of the copepod assemblage in Daya Bay during September 30 to October 2, 2014, were studied based on gut pigment analysis. Small copepods (body length &amp;lt; 1.5 mm) including Paracalanus parvus, Temora turbinata, Acrocalanus gibber, Temora stylifera, Euterpe acutifrons, and Acrocalanus gracilis, accounted for 73.9–100% of the total copepod abundance. The copepod assemblage generally exhibited a diurnal feeding pattern, characterized by a higher gut pigment content and ingestion rate during the daytime, consistent with variation in the ambient Chl α concentration. Fifty-five percent of the phytoplankton standing stock per day was consumed by the copepod assemblage, wherein diatoms, prymnesiophytes, and cyanobacteria were the main prey items with average contributions of 19.4–32.9% to the gut pigment contents. The copepod assemblage showed a strong feeding preference for prymnesiophytes, a weak feeding preference for diatoms, and avoidance of cyanobacteria. These results suggest a strong top-down control on phytoplankton community, especially on small groups from small copepods in the Daya Bay ecosystem.

Cellular and physiological circadian mechanisms drive diurnal cell proliferation and expansion of white adipose tissue

Hyperplastic expansion of white adipose tissue (WAT) relies in part on the proliferation of adipocyte precursor cells residing in the stromal vascular cell fraction (SVF) of WAT. This study reveals a circadian clock- and feeding-induced diurnal pattern of cell proliferation in the SVF of visceral and subcutaneous WAT in vivo, with higher proliferation of visceral adipocyte progenitor cells subsequent to feeding in lean mice. Fasting or loss of rhythmic feeding eliminates this diurnal proliferation, while high fat feeding or genetic disruption of the molecular circadian clock modifies the temporal expression of proliferation genes and impinges on diurnal SVF proliferation in eWAT. Surprisingly, high fat diet reversal, sufficient to reverse elevated SVF proliferation in eWAT, was insufficient in restoring diurnal patterns of SVF proliferation, suggesting that high fat diet induces a sustained disruption of the adipose circadian clock. In conclusion, the circadian clock and feeding simultaneously impart dynamic, regulatory control of adipocyte progenitor proliferation, which may be a critical determinant of adipose tissue expansion and health over time.

Effect of Jicama (Pachyrhizus erosus) Fiber on Energy Intake and Adipose Tissue Profiles in Mice Fed with High-Fat Diet

Jicama (Pachyrhizuz erosus, Fabaceae) has been reported to elicit various medicinal benefits against metabolic disturbances. We also have previously demonstrated that extracted jicama fiber (JF) could sustain normoglycemic state in high-sugar diet fed mice. In this present study, we investigated the effectivity of jicama fiber in preventing the dysregulation of energy metabolism as well as adiposity in adult male BALB/c mice fed with a high-fat diet (HFD). Three groups of animals were treated with normal diet (ND), HFD, and HFD in combination with 25% JF (w/w), respectively for 8 weeks ad libitum. Furthermore, food intake, energy intake, water intake, white adipose (WAT) and brown adipose (BAT) tissue mass, kidney and liver weight as well as organ index were determined. Our investigation revealed that JF 25% could preclude the perturbation of circadian feeding and energy intake rhythms caused by HFD but significantly reduced total water intake. JF also effectively counteracted the marked increase of WAT and decrease of BAT weight and its index in HFD fed mice. Furthermore, JF did not significantly alter the weight and index of both kidney and liver in HFD fed mice. This finding suggests that JF could be used as a potent supplement to minimize the disruption of energy homeostasis and obesity caused by HFD.

Time-Restricted Feeding Regulates Circadian Rhythm of Murine Uterine Clock

ABSTRACTBackgroundSkipping breakfast is associated with dysmenorrhea in young women. This suggests that the delay of food intake in the active phase impairs uterine functions by interfering with circadian rhythms.ObjectivesTo examine the relation between the delay of feeding and uterine circadian rhythms, we investigated the effects of the first meal occasion in the active phase on the uterine clock.MethodsZeitgeber time (ZT) was defined as ZT0 (08:45) with lights on and ZT12 (20:45) with lights off. Young female mice (8 wk of age) were divided into 3 groups: group I (ad libitum consumption), group II (time-restricted feeding during ZT12–16, initial 4 h of the active period), and group III (time-restricted feeding during ZT20–24, last 4 h of the active period, a breakfast-skipping model). After 2 wk of dietary restriction, mice in each group were killed at 4-h intervals and the expression profiles of uterine clock genes, Bmal1 (brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1), Per1 (period circadian clock 1), Per2, and Cry1 (cryptochrome 1), were examined.ResultsqPCR and western blot analyses demonstrated synchronized circadian clock gene expression within the uterus. Immunohistochemical analysis confirmed that BMAL1 protein expression was synchronized among the endometrium and myometrium. In groups I and II, mRNA expression of Bmal1 was elevated after ZT12 at the start of the active phase. In contrast, Bmal1 expression was elevated just after ZT20 in group III, showing that the uterine clock rhythm had shifted 8 h backward. The changes in BMAL1 protein expression were confirmed by western blot analysis.ConclusionsThis study is the first to indicate that time-restricted feeding regulates a circadian rhythm of the uterine clock that is synchronized throughout the uterine body. These findings suggest that the uterine clock system is a new candidate to explain the etiology of breakfast skipping–induced uterine dysfunction.