scholarly journals Circadian regulation of metabolism

2014 ◽  
Vol 222 (2) ◽  
pp. R75-R96 ◽  
Author(s):  
Shannon M Bailey ◽  
Uduak S Udoh ◽  
Martin E Young
Keyword(s):  
Nutrient Supply ◽  
Time Of Day ◽  
Circadian Clocks ◽  
Cardiometabolic Disease ◽  
Circadian Regulation ◽  
Disease Development ◽  
Metabolic Processes ◽  
Regulation Of Metabolism ◽  
Behavioral Influences ◽  
Review Current

In association with sleep–wake and fasting–feeding cycles, organisms experience dramatic oscillations in energetic demands and nutrient supply. It is therefore not surprising that various metabolic parameters, ranging from the activity status of molecular energy sensors to circulating nutrient levels, oscillate in time-of-day-dependent manners. It has become increasingly clear that rhythms in metabolic processes are not simply in response to daily environmental/behavioral influences, but are driven in part by cell autonomous circadian clocks. By synchronizing the cell with its environment, clocks modulate a host of metabolic processes in a temporally appropriate manner. The purpose of this article is to review current understanding of the interplay between circadian clocks and metabolism, in addition to the pathophysiologic consequences of disruption of this molecular mechanism, in terms of cardiometabolic disease development.

scholarly journals Neurogenetic basis for circadian regulation of metabolism by the hypothalamus

2019 ◽  
Vol 33 (17-18) ◽  
pp. 1136-1158 ◽  
Author(s):  
Jonathan Cedernaes ◽  
Nathan Waldeck ◽  
Joseph Bass
Keyword(s):  
Circadian Regulation ◽  
Regulation Of Metabolism

Circadian Timekeeping in Anticancer Therapeutics: An Emerging Vista of Chronopharmacology Research

2021 ◽  
Vol 22 ◽  
Author(s):  
Alekhya Puppala ◽  
Sourbh Rankawat ◽  
Sandipan Ray
Keyword(s):  
Drug Metabolism ◽  
Circadian Clock ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Cancer Biology ◽  
Anticancer Therapy ◽  
Time Of Day ◽  
Circadian Regulation ◽  
Cancer Management ◽  
Anticancer Therapeutics

Background: Intrinsic rhythms in host and cancer cells play an imperative role in tumorigenesis and anticancer therapy. Circadian medicine in cancer is principally reliant on the control of growth and development of cancer cells or tissues by targeting the molecular clock and implementing time-of-day-based anticancer treatments for therapeutic improvements. In recent years, based on extensive high-throughput studies, we witnessed the arrival of several drugs and drug-like compounds that can modulate circadian timekeeping for therapeutic gain in cancer management. Objective: This perspective article intends to illustrate the current trends in circadian medicine in cancer, focusing on clock-modulating pharmacological compounds and circadian regulation of anticancer drug metabolism and efficacy. Scope and Approach: Considering the critical roles of the circadian clock in metabolism, cell signaling, and apoptosis, chronopharmacology research is exceedingly enlightening for understanding cancer biology and improving anticancer therapeutics. In addition to reviewing the relevant literature, we investigated the rhythmic expression of molecular targets for many anticancer drugs frequently used to treat different cancer types. Key Findings and Conclusion: There are adequate empirical pieces of evidence supporting circadian regulation of drug metabolism, transport, and detoxification. Administration of anticancer drugs at specific dosing times can improve their effectiveness and reduce the toxic effects. Moreover, pharmacological modulators of the circadian clock could be used for targeted anticancer therapeutics such as boosting circadian rhythms in the host can markedly reduce the growth and viability of tumors. All in all, precision chronomedicine can offer multiple advantages over conventional anticancer therapy.

30 - Multiomics Profiling of Rat Offspring Exposed to Gestational Diabetes Reveals Cardiometabolic Disease Development With Age

2019 ◽  
Vol 43 (7) ◽  
pp. S12
Author(s):  
STEPHANIE M. Kereliuk ◽  
Prasoon Agarwal ◽  
Laura Cole ◽  
Bo Xiang ◽  
Mario Fonseca ◽  
...  
Keyword(s):  
Gestational Diabetes ◽  
Cardiometabolic Disease ◽  
Disease Development ◽  
Rat Offspring

scholarly journals Interactions between endocrine and circadian systems

2013 ◽  
Vol 52 (1) ◽  
pp. R1-R16 ◽  
Author(s):  
Anthony H Tsang ◽  
Johanna L Barclay ◽  
Henrik Oster
Keyword(s):  
Cognitive Performance ◽  
Hormonal Regulation ◽  
Circadian Clocks ◽  
Circadian Regulation ◽  
Metabolic Homeostasis ◽  
Peripheral Tissues ◽  
Hormonal Factors ◽  
Circadian Timing ◽  
Downstream Processes ◽  
The Brain

In most species, endogenous circadian clocks regulate 24-h rhythms of behavior and physiology. Clock disruption has been associated with decreased cognitive performance and increased propensity to develop obesity, diabetes, and cancer. Many hormonal factors show robust diurnal secretion rhythms, some of which are involved in mediating clock output from the brain to peripheral tissues. In this review, we describe the mechanisms of clock–hormone interaction in mammals, the contribution of different tissue oscillators to hormonal regulation, and how changes in circadian timing impinge on endocrine signalling and downstream processes. We further summarize recent findings suggesting that hormonal signals may feed back on circadian regulation and how this crosstalk interferes with physiological and metabolic homeostasis.

scholarly journals Expansion of the circadian transcriptome in Brassica rapa and genome-wide diversification of paralog expression patterns

2020 ◽  
Author(s):  
Kathleen Greenham ◽  
Ryan C. Sartor ◽  
Stevan Zorich ◽  
Ping Lou ◽  
Todd C. Mockler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brassica Rapa ◽  
Regulatory Network ◽  
Time Course ◽  
Expression Patterns ◽  
Time Of Day ◽  
Circadian Regulation ◽  
Genome Wide ◽  
Circadian Control ◽  
Gene Regulatory

AbstractAn important challenge of crop improvement strategies is assigning function to paralogs in polyploid crops. Gene expression is one method for determining the activity of paralogs; however, the majority of transcript abundance data represents a static point that does not consider the spatial and temporal dynamics of the transcriptome. Studies in Arabidopsis have estimated up to 90% of the transcriptome to be under diel or circadian control depending on the condition. As a result, time of day effects on the transcriptome have major implications on how we characterize gene activity. In this study, we aimed to resolve the circadian transcriptome in the polyploid crop Brassica rapa and explore the fate of multicopy orthologs of Arabidopsis circadian regulated genes. We performed a high-resolution time course study with 2 h sampling density to capture the genes under circadian control. Strikingly, more than two-thirds of expressed genes exhibited rhythmicity indicative of circadian regulation. To compare the expression patterns of paralogous genes, we developed a program in R called DiPALM (Differential Pattern Analysis by Linear Models) that analyzes time course data to identify transcripts with significant pattern differences. Using DiPALM, we identified genome-wide divergence of expression patterns among retained paralogs. Cross-comparison with a previously generated diel drought experiment in B. rapa revealed evidence for differential drought response for these diverging paralog pairs. Using gene regulatory network models we compared transcription factor targets between B. rapa and Arabidopsis circadian networks to reveal additional evidence for divergence in expression between B. rapa paralogs that may be driven in part by variation in conserved non coding sequences. These findings provide new insight into the rapid expansion and divergence of the transcriptional network in a polyploid crop and offer a new method for assessing paralog activity at the transcript level.SignificanceThe circadian regulation of the transcriptome leads to time of day changes in gene expression that coordinates environmental conditions with physiological responses. Brassica rapa, a morphologically diverse crop species, has undergone whole genome triplication since diverging from Arabidopsis resulting in an expansion of gene copy number. To examine how this expansion has influenced the circadian transcriptome we developed a new method for comparing gene expression patterns. This method facilitated the discovery of genome-wide expansion of expression patterns for genes present in multiple copies and divergence in temporal abiotic stress response. We find support for conserved sequences outside the gene body contributing to these expression pattern differences and ultimately generating new connections in the gene regulatory network.

scholarly journals A circadian clock in the blood-brain barrier regulates xenobiotic efflux from the brain

2017 ◽  
Author(s):  
Shirley L. Zhang ◽  
Zhifeng Yue ◽  
Denice M. Arnold ◽  
Amita Sehgal
Keyword(s):  
Gap Junctions ◽  
Blood Brain Barrier ◽  
Time Of Day ◽  
Brain Barrier ◽  
Circadian Regulation ◽  
List Type ◽  
Intracellular Magnesium ◽  
Therapeutic Implications ◽  
Blood Brain ◽  
The Central Nervous System

HighlightsThe Drosophila BBB displays a circadian rhythm of permeabilityCyclic efflux driven by a clock in the BBB underlies the permeability rhythmCircadian control is non-cell-autonomous via gap junction regulation of [Mg2+]iAn anti-seizure drug is more effective when administered at nightSummaryEndogenous circadian rhythms are thought to modulate responses to external factors, but mechanisms that confer time-of-day differences in organismal responses to environmental insults / therapeutic treatments are poorly understood. Using a xenobiotic, we find that permeability of the Drosophila “blood”-brain barrier (BBB) is higher at night. The permeability rhythm is driven by circadian regulation of efflux and depends upon a molecular clock in the perineurial glia of the BBB, although efflux transporters are restricted to subperineurial glia (SPG). We show that transmission of circadian signals across the layers requires gap junctions, which are expressed cyclically. Specifically, during nighttime gap junctions reduce intracellular magnesium ([Mg2+]i), a positive regulator of efflux, in SPG. Consistent with lower nighttime efflux, nighttime administration of the anti-epileptic phenytoin is more effective at treating a Drosophila seizure model. These findings identify a novel mechanism of circadian regulation and have therapeutic implications for drugs targeted to the central nervous system.

scholarly journals Host circadian clocks do not set the schedule for the within-host replication of malaria parasites

2020 ◽  
Vol 287 (1932) ◽  
pp. 20200347
Author(s):  
Aidan J. O'Donnell ◽  
Kimberley F. Prior ◽  
Sarah E. Reece
Keyword(s):  
Time Of Day ◽  
Circadian Clocks ◽  
Host Feeding ◽  
Malaria Parasites ◽  
Disease Symptoms ◽  
Transmission Investment ◽  
Clock Proteins ◽  
Clock Mutant ◽  
Feeding Rhythms ◽  
Parasite Replication

Circadian clocks coordinate organisms' activities with daily cycles in their environment. Parasites are subject to daily rhythms in the within-host environment, resulting from clock-control of host activities, including immune responses. Parasites also exhibit rhythms in their activities: the timing of within-host replication by malaria parasites is coordinated to host feeding rhythms. Precisely which host feeding-related rhythm(s) parasites align with and how this is achieved are unknown. Understanding rhythmic replication in malaria parasites matters because it underpins disease symptoms and fuels transmission investment. We test if rhythmicity in parasite replication is coordinated with the host's feeding-related rhythms and/or rhythms driven by the host's canonical circadian clock. We find that parasite rhythms coordinate with the time of day that hosts feed in both wild-type and clock-mutant hosts, whereas parasite rhythms become dampened in clock-mutant hosts that eat continuously. Our results hold whether infections are initiated with synchronous or with desynchronized parasites. We conclude that malaria parasite replication is coordinated to rhythmic host processes that are independent of the core-clock proteins PERIOD 1 and 2; most likely, a periodic nutrient made available when the host digests food. Thus, novel interventions could disrupt parasite rhythms to reduce their fitness, without interference by host clock-controlled homeostasis.

scholarly journals DOUBLETIME Plays a Noncatalytic Role To Mediate CLOCK Phosphorylation and Repress CLOCK-Dependent Transcription within the Drosophila Circadian Clock

2009 ◽  
Vol 29 (6) ◽  
pp. 1452-1458 ◽  
Author(s):  
Wangjie Yu ◽  
Hao Zheng ◽  
Jeffrey L. Price ◽  
Paul E. Hardin
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Catalytic Activity ◽  
Circadian Clock ◽  
Transcriptional Repression ◽  
Protein Complexes ◽  
Time Of Day ◽  
Feedback Loops ◽  
Circadian Clocks ◽  
Synthesis Activity

ABSTRACT Circadian clocks keep time via gene expression feedback loops that are controlled by time-of-day-specific changes in the synthesis, activity, and degradation of transcription factors. Within the Drosophila melanogaster circadian clock, DOUBLETIME (DBT) kinase is necessary for the phosphorylation of PERIOD (PER), a transcriptional repressor, and CLOCK (CLK), a transcriptional activator, as CLK-dependent transcription is being repressed. PER- and DBT-containing protein complexes feed back to repress CLK-dependent transcription, but how DBT promotes PER and CLK phosphorylation and how PER and CLK phosphorylation contributes to transcriptional repression have not been defined. Here, we show that DBT catalytic activity is not required for CLK phosphorylation or transcriptional repression and that PER phosphorylation is dispensable for repressing CLK-dependent transcription. These results support a model in which DBT plays a novel noncatalytic role in recruiting additional kinases that phosphorylate CLK, thereby repressing transcription. A similar mechanism likely operates in mammals, given the conserved activities of PER, DBT, and CLK orthologs.

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