Health Benefits of Dietary Chronobiotics: Beyond Resynchronizing Internal Clocks

2021 ◽  
Author(s):  
Junqing Huang ◽  
Muwen Lu ◽  
Chi-Tang Ho
Keyword(s):  
Biological Activity ◽  
Circadian Clock ◽  
Health Benefits ◽  
Whole Body ◽  
Hormone Release ◽  
Metabolic Processes ◽  
Activity Rhythms ◽  
Enzyme Functions ◽  
External Signals

The internal circadian clock in mammals drives whole-body biological activity rhythms. The clock reflects changes in external signals by controlling enzyme functions and hormone release involved in metabolic processes. Thus,...

scholarly journals Genetic redundancy strengthens the circadian clock leading to a narrow entrainment range

2013 ◽  
Vol 10 (84) ◽  
pp. 20130221 ◽  
Author(s):  
A. Erzberger ◽  
G. Hampp ◽  
A. E. Granada ◽  
U. Albrecht ◽  
H. Herzel
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
Genetic Network ◽  
Circadian Clocks ◽  
Mutant Mice ◽  
Nonlinear Phenomena ◽  
Genetic Redundancy ◽  
Activity Rhythms ◽  
Almost All ◽  
External Signals

Circadian clocks are internal timekeepers present in almost all organisms. Driven by a genetic network of highly conserved structure, they generate self-sustained oscillations that entrain to periodic external signals such as the 24 h light–dark cycle. Vertebrates possess multiple, functionally overlapping homologues of the core clock genes. Furthermore, vertebrate clocks entrain to a range of periods three times as narrow as that of other organisms. We asked whether genetic redundancies play a role in governing entrainment properties and analysed locomotor activity rhythms of genetically modified mice lacking one set of clock homologues. Exposing them to non-24 h light–dark cycles, we found that the mutant mice have a wider entrainment range than the wild types. Spectral analysis furthermore revealed nonlinear phenomena of periodically forced self-sustained oscillators for which the entrainment range relates inversely to oscillator amplitude. Using the forced oscillator model to explain the observed differences in entrainment range between mutant and wild-type mice, we sought to quantify the overall oscillator amplitude of their clocks from the activity rhythms and found that mutant mice have weaker circadian clocks than wild types. Our results suggest that genetic redundancy strengthens the circadian clock leading to a narrow entrainment range in vertebrates.

scholarly journals CikA, an Input Pathway Component, Senses the Oxidized Quinone Signal to Generate Phase Delays in the Cyanobacterial Circadian Clock

2020 ◽  
Vol 35 (3) ◽  
pp. 227-234 ◽  
Author(s):  
Pyonghwa Kim ◽  
Brianna Porr ◽  
Tetsuya Mori ◽  
Yong-Sung Kim ◽  
Carl H. Johnson ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Time Of Day ◽  
Fine Tuning ◽  
Circadian Oscillation ◽  
Clock Proteins ◽  
Entrainment Process ◽  
Central Oscillator ◽  
External Signals ◽  
Full Synchronization

The circadian clock is a timekeeping system in most organisms that keeps track of the time of day. The rhythm generated by the circadian oscillator must be constantly synchronized with the environmental day/night cycle to make the timekeeping system truly advantageous. In the cyanobacterial circadian clock, quinone is a biological signaling molecule used for entraining and fine-tuning the oscillator, a process in which the external signals are transduced into biological metabolites that adjust the phase of the circadian oscillation. Among the clock proteins, the pseudo-receiver domain of KaiA and CikA can sense external cues by detecting the oxidation state of quinone, a metabolite that reflects the light/dark cycle, although the molecular mechanism is not fully understood. Here, we show the antagonistic phase shifts produced by the quinone sensing of KaiA and CikA. We introduced a new cyanobacterial circadian clock mixture that includes an input component in vitro. KaiA and CikA cause phase advances and delays, respectively, in this circadian clock mixture in response to the quinone signal. In the entrainment process, oxidized quinone modulates the functions of KaiA and CikA, which dominate alternatively at day and night in the cell. This in turn changes the phosphorylation state of KaiC—the central oscillator in cyanobacteria—ensuring full synchronization of the circadian clock. Moreover, we reemphasize the mechanistic input functionality of CikA, contrary to other reports that focus only on its output action.

scholarly journals Flavonoids and Phenolic Acids from Oregano: Occurrence, Biological Activity and Health Benefits

Plants ◽  
2017 ◽  
Vol 7 (1) ◽  
pp. 2 ◽  
Author(s):  
Erick Gutiérrez-Grijalva ◽  
Manuel Picos-Salas ◽  
Nayely Leyva-López ◽  
Marilyn Criollo-Mendoza ◽  
Gabriela Vazquez-Olivo ◽  
...  
Keyword(s):  
Biological Activity ◽  
Phenolic Acids ◽  
Health Benefits

Ventromedial hypothalamic lesions impair glucoregulation in response to endotoxin

1997 ◽  
Vol 272 (5) ◽  
pp. R1525-R1531 ◽  
Author(s):  
J. P. Lynch ◽  
M. M. Wojnar ◽  
C. H. Lang
Keyword(s):  
Metabolic Response ◽  
Plasma Concentrations ◽  
Ventromedial Hypothalamus ◽  
Whole Body ◽  
Tnf Alpha ◽  
Hormone Release ◽  
Glucose Flux ◽  
Bilateral Lesions ◽  
Stimulation Of

The purpose of the present study was to determine the role of the ventromedial hypothalamus (VMH) in regulating counter-regulatory hormone release and the increase in glucose flux that is observed after injection of endotoxin [lipopolysaccharide (LPS)]. Bilateral lesions of the VMH were produced electrolytically 2 wk before the experiment; sham-operated rats served as controls. [3-3H]glucose was infused to assess whole body glucose flux before and for 4 h after intravenous injection of Escherichia coli LPS. In control rats, LPS increased the plasma concentrations of glucose and lactate and the rates of glucose appearance and disappearance. In these animals, LPS also produced sustained elevations in corticosterone, glucagon, and catecholamines. In contrast, the glucose metabolic response to LPS was attenuated by > 50% in VMH-lesioned rats. These changes were associated with a blunted increase in the plasma concentration of glucagon, epinephrine, and norepinephrine in VMH-lesioned rats compared with control animals. There was no difference in the plasma concentrations of corticosterone or TNF-alpha between the two groups after LPS or the responsiveness of sham- and VMH-lesioned rats to an infusion of either glucagon or epinephrine. These data indicate that the VMH plays a central role in regulating the secretion of glucagon and catecholamines and the stimulation of glucose flux after LPS.

scholarly journals Identification and temporal expression of putative circadian clock transcripts in the amphipod crustaceanTalitrus saltator

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2555 ◽  
Author(s):  
Joseph F. O’Grady ◽  
Laura S. Hoelters ◽  
Martin T. Swain ◽  
David C. Wilcockson
Keyword(s):  
Circadian Clock ◽  
Time Course ◽  
Clock Genes ◽  
Biological Clock ◽  
Experimental Manipulation ◽  
Sandy Beaches ◽  
Sequencing Data ◽  
Temporal Expression ◽  
Activity Rhythms ◽  
The Core

BackgroundTalitrus saltatoris an amphipod crustacean that inhabits the supralittoral zone on sandy beaches in the Northeast Atlantic and Mediterranean.T. saltatorexhibits endogenous locomotor activity rhythms and time-compensated sun and moon orientation, both of which necessitate at least one chronometric mechanism. Whilst their behaviour is well studied, currently there are no descriptions of the underlying molecular components of a biological clock in this animal, and very few in other crustacean species.MethodsWe harvested brain tissue from animals expressing robust circadian activity rhythms and used homology cloning and Illumina RNAseq approaches to sequence and identify the core circadian clock and clock-related genes in these samples. We assessed the temporal expression of these genes in time-course samples from rhythmic animals using RNAseq.ResultsWe identified a comprehensive suite of circadian clock gene homologues inT. saltatorincluding the ‘core’ clock genesperiod(Talper),cryptochrome 2(Talcry2),timeless(Taltim),clock(Talclk), andbmal1(Talbmal1). In addition we describe the sequence and putative structures of 23 clock-associated genes including two unusual, extended isoforms of pigment dispersing hormone (Talpdh). We examined time-course RNAseq expression data, derived from tissues harvested from behaviourally rhythmic animals, to reveal rhythmic expression of these genes with approximately circadian period inTalperandTalbmal1. Of the clock-related genes,casein kinase IIβ(TalckIIβ),ebony(Talebony),jetlag(Taljetlag),pigment dispensing hormone(Talpdh),protein phosphatase 1(Talpp1),shaggy(Talshaggy),sirt1(Talsirt1), sirt7 (Talsirt7) and supernumerary limbs (Talslimb) show temporal changes in expression.DiscussionWe report the sequences of principle genes that comprise the circadian clock ofT. saltatorand highlight the conserved structural and functional domains of their deduced cognate proteins. Our sequencing data contribute to the growing inventory of described comparative clocks. Expression profiling of the identified clock genes illuminates tantalising targets for experimental manipulation to elucidate the molecular and cellular control of clock-driven phenotypes in this crustacean.

Physiological and pathophysiological role of the circadian clock system

2012 ◽  
Vol 153 (35) ◽  
pp. 1370-1379 ◽  
Author(s):  
Tamás Halmos ◽  
Ilona Suba
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
Biological Processes ◽  
Metabolic Processes ◽  
Hypothalamic Region ◽  
Clock System ◽  
Treatment And Prevention ◽  
Exact Function ◽  
Essential Components ◽  
Master Clock

It has been well known for ages that in living organisms the rhythmicity of biological processes is linked to the ~ 24-hour light–dark cycle. However, the exact function of the circadian clock system has been explored only in the past decades. It came to light that the photosensitive primary “master clock” is situated in the suprachiasmatic photosensitive nuclei of the special hypothalamic region, and that it is working according to ~24-hour changes of light and darkness. The master clock sends its messages to the peripheral “slave clocks”. In many organs, like pancreatic β-cells, the slave clocks have autonomic functions as well. Two essential components of the clock system are proteins encoded by the CLOCK and BMAL1 genes. CLOCK genes are in interaction with endonuclear receptors such as peroxisoma-proliferator activated receptors and Rev-erb-α, as well as with the hypothalamic-pituitary-adrenal axis, regulating the adaptation to stressors, energy supply, metabolic processes and cardiovascular system. Melatonin, the product of corpus pineale has a significant role in the functions of the clock system. The detailed discovery of the clock system has changed our previous knowledge about the development of many diseases. The most explored fields are hypertension, cardiovascular diseases, metabolic processes, mental disorders, cancers, sleep apnoe and joint disorders. CLOCK genes influence ageing as well. The recognition of the periodicity of biological processes makes the optimal dosing of certain drugs feasible. The more detailed discovery of the interaction of the clock system might further improve treatment and prevention of many disorders. Orv. Hetil., 2012, 153, 1370–1379.

scholarly journals The synthesis of [14C]streptozotocin and its distribution and excretion in the rat

1974 ◽  
Vol 142 (3) ◽  
pp. 673-683 ◽  
Author(s):  
Eric H. Karunanayake ◽  
David J. Hearse ◽  
Graham Mellows
Keyword(s):  
Biological Activity ◽  
Tissue Distribution ◽  
Renal Clearance ◽  
Dose Response ◽  
Whole Body ◽  
Response Curves ◽  
Intestinal Excretion ◽  
Metabolic Transformation ◽  
Distribution Studies

[14C]Streptozotocin was synthesized specifically labelled at three positions in the molecule. The biological activity of synthetic streptozotocin was characterised by studies in vivo of its diabetogenic activity and its dose–response curves. After this characterization the excretion pattern of all three labelled forms of streptozotocin was studied. With [1-14C]streptozotocin and [2′-14C]streptozotocin the injected radioactivity was excreted (approx. 70% and 80% respectively) mainly in the urine, the greater part of the excretion occurring in the first 6h period; small amounts (approx. 9% and 8% respectively) were found in the faeces. In contrast, with [3′-methyl-14C]streptozotocin a much smaller proportion (approx. 42%) of the injected radioactivity was excreted in the urine, the major proportion appearing in the first 6h, whereas approx. 53% of the injected radioactivity was retained in the carcasses. In whole-body radioautographic studies very rapid renal clearance and hepatic accumulation of the injected radioactivity was observed with all three labelled forms of the drug. There was some evidence for biliary and intestinal excretion. Major differences were apparent in the tissue-distribution studies, with each of the three labelled forms, particularly with [3′-methyl-14C]streptozotocin. There was no accumulation of [1-14C]streptozotocin in the pancreas for the 6h period after administration. However, with [3′-methyl-14C]streptozotocin (and also [2′-14C]streptozotocin) there was evidence of some pancreatic accumulation after 2h. The results indicate that streptozotocin is subjected to considerable metabolic transformation and to rapid renal clearance. The implication of these suggestions is evaluated with particular reference to the diabetogenic action of streptozotocin.

scholarly journals The Development and Decay of the Circadian Clock in Drosophila melanogaster

2019 ◽  
Vol 1 (4) ◽  
pp. 489-500
Author(s):  
Jia Zhao ◽  
Guy Warman ◽  
James Cheeseman
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
Firefly Luciferase ◽  
Whole Body ◽  
Drosophila Model ◽  
Central Clock ◽  
Development And Aging ◽  
Central Oscillator ◽  
The Brain ◽  
Insight Into

The way in which the circadian clock mechanism develops and decays throughout life is interesting for a number of reasons and may give us insight into the process of aging itself. The Drosophila model has been proven invaluable for the study of the circadian clock and development and aging. Here we review the evidence for how the Drosophila clock develops and changes throughout life, and present a new conceptual model based on the results of our recent work. Firefly luciferase lines faithfully report the output of known clock genes at the central clock level in the brain and peripherally throughout the whole body. Our results show that the clock is functioning in embryogenesis far earlier than previously thought. This central clock in the fly remains robust throughout the life of the animal and only degrades immediately prior to death. However, at the peripheral (non-central oscillator level) the clock shows weakened output as the animal ages, suggesting the possibility of the breakdown in the cohesion of the circadian network.

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