scholarly journals Circadian rhythms of gastrointestinal function are regulated by both central and peripheral oscillators

2012 ◽  
Vol 303 (4) ◽  
pp. G461-G473 ◽  
Author(s):  
Jaclyn N. Malloy ◽  
Jiffin K. Paulose ◽  
Ye Li ◽  
Vincent M. Cassone
Keyword(s):  
Circadian Rhythms ◽  
Ex Vivo ◽  
Circadian Clocks ◽  
Constant Darkness ◽  
Restricted Feeding ◽  
Chemical Sympathectomy ◽  
Surgical Ablation ◽  
Peripheral Oscillators ◽  
Ad Libitum ◽  
6 Hydroxydopamine

Circadian clocks are responsible for daily rhythms in a wide array of processes, including gastrointestinal (GI) function. These are vital for normal digestive rhythms and overall health. Previous studies demonstrated circadian clocks within the cells of GI tissue. The present study examines the roles played by the suprachiasmatic nuclei (SCN), master circadian pacemaker for overt circadian rhythms, and the sympathetic nervous system in regulation of circadian GI rhythms in the mouse Mus musculus . Surgical ablation of the SCN abolishes circadian locomotor, feeding, and stool output rhythms when animals are presented with food ad libitum, while restricted feeding reestablishes these rhythms temporarily. In intact mice, chemical sympathectomy with 6-hydroxydopamine has no effect on feeding and locomotor rhythmicity in light-dark cycles or constant darkness but attenuates stool weight and stool number rhythms. Again, however, restricted feeding reestablishes rhythms in locomotor activity, feeding, and stool output rhythms. Ex vivo, intestinal tissue from PER2::LUC transgenic mice expresses circadian rhythms of luciferase bioluminescence. Chemical sympathectomy has little effect on these rhythms, but timed administration of the β-adrenergic agonist isoproterenol causes a phase-dependent shift in PERIOD2 expression rhythms. Collectively, the data suggest that the SCN are required to maintain feeding, locomotor, and stool output rhythms during ad libitum conditions, acting at least in part through daily activation of sympathetic activity. Even so, this input is not necessary for entrainment to timed feeding, which may be the province of oscillators within the intestines themselves or other components of the GI system.

scholarly journals Oxytocinergic cells of the posterior hypothalamic paraventricular nucleus participate in the food entrained clock

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mario Caba ◽  
Enrique Meza ◽  
Carolina Escobar ◽  
Angeles Jiménez ◽  
Mario Daniel Caba-Flores ◽  
...  
Keyword(s):  
Food Intake ◽  
Hypothalamic Nucleus ◽  
Restricted Feeding ◽  
Adult Rats ◽  
Peripheral Oscillators ◽  
Food Anticipatory Activity ◽  
Ad Libitum ◽  
Anticipatory Activity ◽  
Oxytocinergic Cells

AbstractThe mechanisms underlying food anticipatory activity are still poorly understood. Here we explored the role of oxytocin (OT) and the protein c-Fos in the supraoptic nucleus (SON), medial (PVNm) and posterior (PVNp) regions of the paraventricular hypothalamic nucleus. Adult rats were assigned to one of four groups: scheduled restricted feeding (RF), ad libitum (AL), fasting after restricted feeding (RF-F), to explore the possible persistence of oscillations, or ad libitum fasted (AL-F). In the SON and in the PVNm, OT cells were c-Fos positive after food intake; in contrast, OT cells in the PVNp showed c-Fos activation in anticipation to food access, which persisted in RF-F subjects. We conclude that OT and non-OT cells of the SON and PVNm may play a role as recipients of the entraining signal provided by food intake, whereas those of the PVNp which contain motor preautonomic cells that project to peripheral organs, may be involved in the hormonal and metabolic anticipatory changes in preparation for food presentation and thus, may be part of a link between central and peripheral oscillators. In addition, due to their persistent activation they may participate in the neuronal network for the clock mechanism that leads to food entrainment.

scholarly journals Oxytocinergic Cells of the Posterior Hypothalamic Paraventricular Nucleus Participate in the Food Entrained Clock

2021 ◽  
Author(s):  
Mario Caba ◽  
Enrique Meza ◽  
Carolina Escobar ◽  
Angeles Jiménez ◽  
Mario Daniel Caba-Flores ◽  
...  
Keyword(s):  
Food Intake ◽  
Hypothalamic Nucleus ◽  
Restricted Feeding ◽  
Adult Rats ◽  
Peripheral Oscillators ◽  
Food Anticipatory Activity ◽  
Ad Libitum ◽  
Anticipatory Activity ◽  
Oxytocinergic Cells

Abstract The mechanisms underlying food anticipatory activity is still not well understood. Here we explored the role of oxytocin (OT) and the protein c-Fos in the supraoptic nucleus (SON) and in the medial (PVNm) and posterior (PVNp) regions of the paraventricular hypothalamic nucleus. Adult rats were assigned to one of four groups: scheduled restricted feeding (RF), Ad libitum (AL), fasting after restricted feeding (RF-F), to explore the possible persistence of oscillations, or Ad libitum fasted (AL-F). In the SON and in the PVNm, OT cells were c-Fos positive after food intake; contrasting, OT cells in the PVNp showed c-Fos activation in anticipation to food access, which persisted in RF-F subjects. We conclude that OT cells of the SON and PVNm may play a role as recipients of the entraining signal provided by food intake, whereas those of the PVNp which contain motor preautonomic cells that project to peripheral organs, may be involved in the hormonal and metabolic anticipatory changes in preparation for food presentation and thus, may be part of a link between central and peripheral oscillators. In addition, due to their persistent activation they may participate in the neuronal network for the clock mechanism that leads to food entrainment.

scholarly journals Melatonin Adjusts the Phase of Mouse Circadian Clocks in the Cornea Both Ex Vivo and In Vivo

2021 ◽  
pp. 074873042110323
Author(s):  
Alex V. Huynh ◽  
Ethan D. Buhr
Keyword(s):  
Mammalian Cells ◽  
Ex Vivo ◽  
Circadian Clocks ◽  
Constant Darkness ◽  
Environmental Cues ◽  
Dark Cycle ◽  
Environmental Light ◽  
Advanced Phase ◽  
Different Tissues

The presence of an endogenous circadian clock within most mammalian cells is associated with the amazing observation that within a given tissue, these clocks are largely in synchrony with each other. Different tissues use a variety of systemic or environmental cues to precisely coordinate the phase of these clocks. The cornea is a unique tissue in that it is largely isolated from the direct blood supply that most tissues experience, it is transparent to visible light, and it is exposed directly to environmental light and temperature. Melatonin is a hormone that has been implicated in regulation of the cornea’s circadian clocks. Here, we analyze the ability of rhythmic melatonin to entrain corneas ex vivo, and analyze the phase of corneal circadian clocks in vivo both in light: dark cycles and in constant darkness. We find that the presence of a retina from a melatonin-proficient mouse strain, C3Sn, can photoentrain the circadian clocks of a co-cultured mouse cornea, but a retina from a melatonin-deficient strain, C57Bl/6, cannot. Furthermore, pharmacologic blockade of melatonin or use of a retina with advanced retinal degeneration, Pde6brd1, blocks the photoentraining effect. Corneal circadian clocks in vivo adopt an advanced phase in C3Sn mice compared with C57Bl/6, but the circadian clocks in the liver are unaffected. This observation is not attributable to a shorter endogenous period of the cornea or behavior between the strains. Some transcripts of circadian genes in the corneas of C3Sn mice also show an advanced phase of expression in a light: dark cycle, while the transcript of Per2 exhibits a light-dependent transient induction at the onset of darkness. We conclude that melatonin acts as a phase modifying factor in a rhythmic manner for the circadian clocks of the cornea.

scholarly journals miR-210 controls the evening phase of circadian locomotor rhythms through repression of Fasciclin 2

2018 ◽  
Author(s):  
Wesley Leigh ◽  
Zhenxing Liu ◽  
Xiaoge Nian ◽  
Yong Zhang
Keyword(s):  
Cell Adhesion ◽  
Circadian Rhythms ◽  
Binding Site ◽  
Environmental Changes ◽  
Fruit Flies ◽  
Circadian Clocks ◽  
Phase Advance ◽  
Constant Darkness ◽  
Circadian Regulation ◽  
Anticipatory Behavior

AbstractCircadian clocks control the timing of animal behavior rhythms to anticipate daily environmental changes. Fruit flies gradually increase their activity and reach a peak of activity around dawn and dusk. microRNAs are small non-coding RNAs that play important roles in post-transcriptional regulation. Here we identify Drosophila miR-210 as a critical regulator of circadian rhythms. Under light-dark conditions, flies lacking miR-210 (miR-210KO) exhibit a dramatic phase advance of evening anticipatory behavior about 2 hours. However, circadian rhythms and molecular pacemaker function are intact in miR-210KO flies under constant darkness. Furthermore, we identify that miR-210 determines the evening phase of activity through repression of the cell adhesion molecule Fasciclin 2 (Fas2). Ablation of the miR-210 binding site within the 3’ UTR of Fas2 (Fas2ΔmiR-210) by CRISPR-Cas9 advances the evening phase as in miR-210KO. Indeed, miR-210 genetically interacts with Fas2. Moreover, Fas2 abundance is significantly increased in the optic lobe of miR-210KO and Fas2ΔmiR-210. In addition, overexpression of Fas2 in the miR-210 expressing cells recapitulates the phase advance behavior phenotype of miR-210KO. Together, these results reveal a novel mechanism by which miR-210 regulates circadian locomotor behavior.Author summaryCircadian clocks control the timing of animal physiology. Drosophila has been a powerful model in understanding the mechanisms of circadian regulation. Fruit flies anticipate daily environmental changes and exhibit two peaks of locomotor activity around dawn and dusk. Here we identify miR-210 as a critical regulator of evening anticipatory behavior. Depletion of miR-210 in flies advances evening anticipation. Futhermore, we identify the cell adhesion molecular Fas2 as miR-210’s target in circadian regulation. Fas2 abundance is increased in fly brain lacking of miR-210. Using CRISPR-Cas9 genome editing method, we deleted the miR-210 binding site on 3’ untranslated region of Fas2 and observed similar phenotype as miR-210 mutants. Altogether, our results indicate a novel mechanism of miR-210 in regulation of circadian anticipatory behavior through inhibition of Fas2.

scholarly journals Differential impacts of the head onPlatynereis dumeriliiperipheral circadian rhythms

2019 ◽  
Author(s):  
Enrique Arboleda ◽  
Martin Zurl ◽  
Kristin Tessmar-Raible
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Clock Genes ◽  
Functional Model ◽  
Circadian Clocks ◽  
Constant Darkness ◽  
Dark Cycle ◽  
Peripheral Tissues ◽  
Platynereis Dumerilii ◽  
Strong Control

AbstractBackgroundThe marine bristle wormPlatynereis dumeriliiis a useful functional model system for the study of the circadian clock and its interplay with others, e.g. circalunar clocks. The focus has so far been on the worm’s head. However, behavioral and physiological cycles in other animals typically arise from the coordination of circadian clocks located in the brain and in peripheral tissues. Here we focus on peripheral circadian rhythms and clocks, revisit and expand classical circadian work on the worm’s chromatophores, investigate locomotion as read-out and include molecular analyses.ResultsWe establish that different pieces of the trunk exhibit synchronized, robust oscillations of core circadian clock genes. These circadian core clock transcripts are under strong control of the light-dark cycle, quickly losing synchronized oscillation under constant darkness, irrespective of the absence or presence of heads. Different wavelengths are differently effective in controlling the peripheral molecular synchronization. We have previously shown that locomotor activity is under circadian clock control. Here we show that upon decapitation it still follows the light-dark cycle, but does not free-run under constant darkness. We also observe the rhythmicity of pigments in the worm’s individual chromatophores, confirming that chromatophore size changes follow a circadian pattern. These size changes continue under constant darkness, but cannot be re-entrained by light upon decapitation.ConclusionsHere we provide the first basic characterization of the peripheral circadian clock ofPlatynereis dumerilii. In the absence of the head, light is essential as a major synchronization cue for peripheral molecular and locomotor circadian rhythms. Circadian changes in chromatophore size can however continue for several days in the absence of light/dark changes and the head. Thus, the dependence on the head depends on the type of peripheral rhythm studied. These data show that peripheral circadian rhythms and clocks should be considered when investigating the interactions of clocks with different period lengths, a notion likely also true for other organisms with circadian and non-circadian clocks.

scholarly journals Natural food intake patterns have little synchronizing effect on peripheral circadian clocks

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiaobin Xie ◽  
Ayaka Kukino ◽  
Haley E. Calcagno ◽  
Alec M. Berman ◽  
Joseph P. Garner ◽  
...  
Keyword(s):  
Food Intake ◽  
Circadian Rhythms ◽  
Submandibular Gland ◽  
Activity Cycle ◽  
Circadian Clocks ◽  
Dark Cycle ◽  
Liver And Kidney ◽  
Peripheral Clocks ◽  
Ad Libitum ◽  
Rest Activity

Abstract Background Circadian rhythms across mammalian tissues are coordinated by a master clock in the suprachiasmatic nucleus (SCN) that is principally entrained by light-dark cycles. Prior investigations have shown, however, that time-restricted feeding (TRF)—daily alternation of fasting and food availability—synchronizes peripheral clocks independent of the light-dark cycle and of the SCN. This has led to the idea that downstream peripheral clocks are entrained indirectly by food intake rhythms. However, TRF is not a normal eating pattern, and it imposes non-physiologic long fasts that rodents do not typically experience. Therefore, we tested whether normal feeding patterns can phase-shift or entrain peripheral tissues by measuring circadian rhythms of the liver, kidney, and submandibular gland in mPer2Luc mice under different food schedules. Results We employed home cage feeders to first measure ad libitum food intake and then to dispense 20-mg pellets on a schedule mimicking that pattern. In both conditions, PER2::LUC bioluminescence peaked during the night as expected. Surprisingly, shifting the scheduled feeding by 12 h advanced peripheral clocks by only 0–3 h, much less than predicted from TRF protocols. To isolate the effects of feeding from the light-dark cycle, clock phase was then measured in mice acclimated to scheduled feeding over the course of 3 months in constant darkness. In these conditions, peripheral clock phases were better predicted by the rest-activity cycle than by the food schedule, contrary to expectation based on TRF studies. At the end of both experiments, mice were exposed to a modified TRF with food provided in eight equally sized meals over 12 h. In the light-dark cycle, this advanced the phase of the liver and kidney, though less so than in TRF with ad libitum access; in darkness, this entrained the liver and kidney but had little effect on the submandibular gland or the rest-activity cycle. Conclusions These data suggest that natural feeding patterns can only weakly affect circadian clocks. Instead, in normally feeding mice, the central pacemaker in the brain may set the phase of peripheral organs via pathways that are independent of feeding behavior.

scholarly journals 117 Functionality of a novel consensus bacterial 6-phytase variant in enhancing phosphorus digestibility in gestating and lactating sows

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 109-109
Author(s):  
Deepak Velayudhan ◽  
Xandra Benthem de Grave ◽  
Katie Waller ◽  
Leon Marchal ◽  
Yueming Dersjant-Li
Keyword(s):  
Soybean Meal ◽  
Random Effect ◽  
Positive Control ◽  
Negative Control ◽  
Combined Effect ◽  
Restricted Feeding ◽  
Sunflower Meal ◽  
Tukey Test ◽  
Lactating Sows ◽  
Ad Libitum

Abstract Two experiments were conducted to determine the efficacy of phytase on apparent total tract digestibility (ATTD) of phosphorus (P) in gestating and lactating sows. In Exp. 1, a total of 40 sows (parity 2–6) at d 78 of gestation were randomly assigned, based on parity, over 4 experimental diets. In Exp. 2, 40 sows (parity 2.0–6.0) at d 4 of lactation were randomly assigned based on parity, over 4 experimental diets. Both studies had a positive control (PC) diet with adequate levels of calcium (Ca) and digestible P (6.5 and 2.5 g/kg and 7.0 and 3.2 g/kg for gestation and lactation diets, respectively), a negative control (NC) diet with low Ca and digestible P levels (5.0 and 1.0 g/kg and 5.0 and 1.5 g/kg for gestation and lactation diets, respectively), and NC supplemented with a novel consensus bacterial 6-phytase variant (PhyG) or a commercial Buttiauxella sp. phytase (PhyB), both at 500 FTU/kg. Diets were corn, soybean meal and sunflower meal based (phytate P of 3.0 g/kg) with restricted feeding during gestation and ad libitum during lactation. In both studies, fecal samples were collected after an adaptation of 14 d on 4 successive days to determine ATTD of P. Data were analyzed using ANOVA, treatment mean comparison using Tukey test using JMP 14. In addition, data from the Exp. 1 and 2 were pooled to further investigate their combined effect, using trial as random effect. In both studies, supplementation of both phytases improved (P < 0.05) ATTD of P vs NC. With data combined from two trials, sows fed PhyG showed greater (P < 0.05) ATTD of P when compared those fed PhyB. In conclusion, PhyG at 500 FTU/kg showed a greater ATTD of P in sows when compared to the PhyB at 500 FTU/kg, when data combined from two trials.

scholarly journals Time-restricted feeding regulates circadian rhythm of murine uterine clock

2021 ◽  
Author(s):  
Takashi Hosono ◽  
Masanori Ono ◽  
Takiko Daikoku ◽  
Michihiro Mieda ◽  
Satoshi Nomura ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Protein Expression ◽  
Western Blot ◽  
Active Phase ◽  
Active Period ◽  
Restricted Feeding ◽  
Group Iii ◽  
Breakfast Skipping ◽  
Group I

Abstract Background Skipping 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. Objective To examine the relationship 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. Methods Zeitgeber time (ZT) was defined as ZT 0 (8:45) with lights on and ZT 12 (20:45) with lights off. Young female mice (8 weeks of age) were divided into 3 groups: group I (ad-libitum feeding), group II (time-restricted feeding during ZT12–16, initial 4 hours of the active period), and group III (time-restricted feeding during ZT20–24, last 4 hours of the active period, a breakfast-skipping model). After two weeks of dietary restriction, mice in each group were sacrificed at 4-hour intervals and the expression profiles of uterine clock genes, Bmal1, Per1, Per2, and Cry1, were examined. Results qPCR 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 hours backward. The changes in Bmal1 protein expression were confirmed by Western blot analysis. Conclusion This 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.

The effects of environmental temperature and method of feeding on the performance and carcass composition of bacon pigs

1967 ◽  
Vol 9 (2) ◽  
pp. 209-218 ◽  
Author(s):  
D. W. Holme ◽  
W. E. Coey
Keyword(s):  
Environmental Temperature ◽  
Average Daily Gain ◽  
Carcass Composition ◽  
Restricted Feeding ◽  
Feed Conversion ◽  
Feeding Method ◽  
Feeding Regimes ◽  
Higher Temperature ◽  
Ad Libitum ◽  
Environmental Temperatures

A trial designed to investigate the effects of two environmental temperatures, three feeding regimes and the interactions between them is described. A temperature of 72° F. was better than one of 54° F. for bacon pigs between 40 lb. and 200 lb. weight. The higher temperature resulted in faster growth, more efficient feed conversion and increased length of carcass. Other carcass characteristics were not significantly altered. Ad libitum feeding resulted in faster growth and fatter carcasses than restricted feeding, but did not have a significant effect on efficiency of feed conversion. When feed intake was restricted, feeding pigs once daily or twice daily resulted in similar performance and carcass composition.There was a significant interaction between environmental temperature and feeding method for average daily gain in that pigs fed ad libitum grew faster at the low temperature and pigs fed restricted amounts of feed grew faster at the high temperature. No other interaction reached significant levels.

Disrupted circadian rhythms in VIP- and PHI-deficient mice

2003 ◽  
Vol 285 (5) ◽  
pp. R939-R949 ◽  
Author(s):  
Christopher S. Colwell ◽  
Stephan Michel ◽  
Jason Itri ◽  
Williams Rodriguez ◽  
J. Tam ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Wheel Running ◽  
Activity Rhythm ◽  
Activity Patterns ◽  
Circadian System ◽  
Diurnal Rhythms ◽  
Constant Darkness ◽  
Light Cycle ◽  
Wild Type ◽  
Deficient Mice

The related neuropeptides vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) are expressed at high levels in the neurons of the suprachiasmatic nucleus (SCN), but their function in the regulation of circadian rhythms is unknown. To study the role of these peptides on the circadian system in vivo, a new mouse model was developed in which both VIP and PHI genes were disrupted by homologous recombination. In a light-dark cycle, these mice exhibited diurnal rhythms in activity which were largely indistinguishable from wild-type controls. In constant darkness, the VIP/PHI-deficient mice exhibited pronounced abnormalities in their circadian system. The activity patterns started ∼8 h earlier than predicted by the previous light cycle. In addition, lack of VIP/PHI led to a shortened free-running period and a loss of the coherence and precision of the circadian locomotor activity rhythm. In about one-quarter of VIP/PHI mice examined, the wheel-running rhythm became arrhythmic after several weeks in constant darkness. Another striking example of these deficits is seen in the split-activity patterns expressed by the mutant mice when they were exposed to a skeleton photoperiod. In addition, the VIP/PHI-deficient mice exhibited deficits in the response of their circadian system to light. Electrophysiological analysis indicates that VIP enhances inhibitory synaptic transmission within the SCN of wild-type and VIP/PHI-deficient mice. Together, the observations suggest that VIP/PHI peptides are critically involved in both the generation of circadian oscillations as well as the normal synchronization of these rhythms to light.

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