The circadian clock and metabolism

2010 ◽  
Vol 120 (2) ◽  
pp. 65-72 ◽  
Author(s):  
Oren Froy
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
The Body ◽  
Suprachiasmatic Nuclei ◽  
Peripheral Tissues ◽  
Environmental Light ◽  
Activity Of Enzymes ◽  
Transcription Activators ◽  
The Relationship ◽  
Daily Changes

Mammals have developed an endogenous circadian clock located in the SCN (suprachiasmatic nuclei) of the anterior hypothalamus that responds to the environmental light–dark cycle. Human homoeostatic systems have adapted to daily changes in a way that the body anticipates the sleep and activity periods. Similar clocks have been found in peripheral tissues, such as the liver, intestine and adipose tissue. Recently it has been found that the circadian clock regulates cellular and physiological functions in addition to the expression and/or activity of enzymes and hormones involved in metabolism. In turn, key metabolic enzymes and transcription activators interact with and affect the core clock mechanism. Animals with mutations in clock genes that disrupt cellular rhythmicity have provided evidence to the relationship between the circadian clock and metabolic homoeostasis. The present review will summarize recent findings concerning the relationship between metabolism and circadian rhythms.

scholarly journals Disruption of Circadian Rhythms: A Crucial Factor in the Etiology of Infertility

2020 ◽  
Vol 21 (11) ◽  
pp. 3943
Author(s):  
Francesca Sciarra ◽  
Edoardo Franceschini ◽  
Federica Campolo ◽  
Daniele Gianfrilli ◽  
Francesco Pallotti ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Clock Genes ◽  
Hormone Secretion ◽  
The Body ◽  
Molecular Networks ◽  
Industrialized Countries ◽  
Suprachiasmatic Nuclei ◽  
Sexual Hormones ◽  
Fine Tune

Infertility represents a growing health problem in industrialized countries. Thus, a greater understanding of the molecular networks involved in this disease could be critical for the development of new therapies. A recent finding revealed that circadian rhythmicity disruption is one of the main causes of poor reproductive outcome. The circadian clock system beats circadian rhythms and modulates several physiological functions such as the sleep-wake cycle, body temperature, heart rate, and hormones secretion, all of which enable the body to function in response to a 24 h cycle. This intricated machinery is driven by specific genes, called “clock genes” that fine-tune body homeostasis. Stress of modern lifestyle can determine changes in hormone secretion, favoring the onset of infertility-related conditions that might reflect disfunctions within the hypothalamic–pituitary–gonadal axis. Consequently, the loss of rhythmicity in the suprachiasmatic nuclei might affect pulsatile sexual hormones release. Herein, we provide an overview of the recent findings, in both animal models and humans, about how fertility is influenced by circadian rhythm. In addition, we explore the complex interaction among hormones, fertility and the circadian clock. A deeper analysis of these interactions might lead to novel insights that could ameliorate the therapeutic management of infertility and related disorders.

scholarly journals Chronobiology and Metabolism: Is Ketogenic Diet Able to Influence Circadian Rhythm?

2021 ◽  
Vol 15 ◽  
Author(s):  
Elena Gangitano ◽  
Lucio Gnessi ◽  
Andrea Lenzi ◽  
David Ray
Keyword(s):  
Gene Expression ◽  
Circadian Rhythm ◽  
Circadian Clock ◽  
Ketogenic Diet ◽  
Clock Genes ◽  
The Body ◽  
Acid Oxidation ◽  
Metabolic Switch ◽  
Peripheral Tissues ◽  
Central Clock

Circadian rhythms underpin most physiological processes, including energy metabolism. The core circadian clock consists of a transcription-translation negative feedback loop, and is synchronized to light-dark cycles by virtue of light input from the retina, to the central clock in the suprachiasmatic nucleus in the hypothalamus. All cells in the body have circadian oscillators which are entrained to the central clock by neural and humoral signals. In addition to light entrainment of the central clock in the brain, it now emerges that other stimuli can drive circadian clock function in peripheral tissues, the major one being food. This can then drive the liver clock to be misaligned with the central brain clock, a situation of internal misalignment with metabolic disease consequences. Such misalignment is prevalent, with shift workers making up 20% of the working population. The effects of diet composition on the clock are not completely clarified yet. High-fat diet and fasting influence circadian expression of clock genes, inducing phase-advance and phase-delay in animal models. Ketogenic diet (KD) is able to induce a metabolic switch from carbohydrate to fatty acid oxidation, miming a fasting state. In recent years, some animal studies have been conducted to investigate the ability of the KD to modify circadian gene expression, and demonstrated that the KD alters circadian rhythm and induces a rearrangement of metabolic gene expression. These findings may lead to new approaches to obesity and metabolic pathologies treatment.

scholarly journals Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis

2021 ◽  
Vol 22 (2) ◽  
pp. 676
Author(s):  
Andy W. C. Man ◽  
Huige Li ◽  
Ning Xia
Keyword(s):  
Circadian Rhythm ◽  
Cardiovascular Diseases ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Therapeutic Target ◽  
Environmental Changes ◽  
Clock Genes ◽  
Vascular System ◽  
Peripheral Tissues ◽  
Inflammatory Processes

Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings have suggested strong correlations between the circadian clock and cardiovascular diseases. Desynchronization between the circadian rhythm and body metabolism contributes to the development of cardiovascular diseases including arteriosclerosis and thrombosis. Circadian rhythms are involved in controlling inflammatory processes and metabolisms, which can influence the pathology of arteriosclerosis and thrombosis. Circadian clock genes are critical in maintaining the robust relationship between diurnal variation and the cardiovascular system. The circadian machinery in the vascular system may be a novel therapeutic target for the prevention and treatment of cardiovascular diseases. The research on circadian rhythms in cardiovascular diseases is still progressing. In this review, we briefly summarize recent studies on circadian rhythms and cardiovascular homeostasis, focusing on the circadian control of inflammatory processes and metabolisms. Based on the recent findings, we discuss the potential target molecules for future therapeutic strategies against cardiovascular diseases by targeting the circadian clock.

scholarly journals Modeling and analysis of the impacts of jet lag on circadian rhythm and its role in tumor growth

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4877 ◽  
Author(s):  
Azka Hassan ◽  
Jamil Ahmad ◽  
Hufsah Ashraf ◽  
Amjad Ali
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Clock Genes ◽  
Damage Control ◽  
Vital Role ◽  
Biochemical Networks ◽  
Jet Lag ◽  
Peripheral Tissues ◽  
Modeling And Analysis ◽  
Circadian Clock Proteins

Circadian rhythms maintain a 24 h oscillation pattern in metabolic, physiological and behavioral processes in all living organisms. Circadian rhythms are organized as biochemical networks located in hypothalamus and peripheral tissues. Rhythmicity in the expression of circadian clock genes plays a vital role in regulating the process of cell division and DNA damage control. The oncogenic protein, MYC and the tumor suppressor, p53 are directly influenced by the circadian clock. Jet lag and altered sleep/wake schedules prominently affect the expression of molecular clock genes. This study is focused on developing a Petri net model to analyze the impacts of long term jet lag on the circadian clock and its probable role in tumor progression. The results depict that jet lag disrupts the normal rhythmic behavior and expression of the circadian clock proteins. This disruption leads to persistent expression of MYC and suppressed expression of p53. Thus, it is inferred that jet lag altered circadian clock negatively affects the expressions of cell cycle regulatory genes and contribute in uncontrolled proliferation of tumor cells.

Achilles-Mediated and Sex-Specific Regulation of Circadian mRNA Rhythms in Drosophila

2019 ◽  
Vol 34 (2) ◽  
pp. 131-143 ◽  
Author(s):  
Jiajia Li ◽  
Renee Yin Yu ◽  
Farida Emran ◽  
Brian E. Chen ◽  
Michael E. Hughes
Keyword(s):  
Circadian Clock ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Clock Genes ◽  
Peripheral Tissues ◽  
Knock Down ◽  
Rhythmic Expression ◽  
The Core ◽  
Physiological Processes ◽  
Specific Regulation

The circadian clock is an evolutionarily conserved mechanism that generates the rhythmic expression of downstream genes. The core circadian clock drives the expression of clock-controlled genes, which in turn play critical roles in carrying out many rhythmic physiological processes. Nevertheless, the molecular mechanisms by which clock output genes orchestrate rhythmic signals from the brain to peripheral tissues are largely unknown. Here we explored the role of one rhythmic gene, Achilles, in regulating the rhythmic transcriptome in the fly head. Achilles is a clock-controlled gene in Drosophila that encodes a putative RNA-binding protein. Achilles expression is found in neurons throughout the fly brain using fluorescence in situ hybridization (FISH), and legacy data suggest it is not expressed in core clock neurons. Together, these observations argue against a role for Achilles in regulating the core clock. To assess its impact on circadian mRNA rhythms, we performed RNA sequencing (RNAseq) to compare the rhythmic transcriptomes of control flies and those with diminished Achilles expression in all neurons. Consistent with previous studies, we observe dramatic upregulation of immune response genes upon knock-down of Achilles. Furthermore, many circadian mRNAs lose their rhythmicity in Achilles knock-down flies, suggesting that a subset of the rhythmic transcriptome is regulated either directly or indirectly by Achilles. These Achilles-mediated rhythms are observed in genes involved in immune function and in neuronal signaling, including Prosap, Nemy and Jhl-21. A comparison of RNAseq data from control flies reveals that only 42.7% of clock-controlled genes in the fly brain are rhythmic in both males and females. As mRNA rhythms of core clock genes are largely invariant between the sexes, this observation suggests that sex-specific mechanisms are an important, and heretofore under-appreciated, regulator of the rhythmic transcriptome.

scholarly journals Entrainment of peripheral clock genes by cortisol

2012 ◽  
Vol 44 (11) ◽  
pp. 607-621 ◽  
Author(s):  
Panteleimon D. Mavroudis ◽  
Jeremy D. Scheff ◽  
Steve E. Calvano ◽  
Stephen F. Lowry ◽  
Ioannis P. Androulakis
Keyword(s):  
Clock Genes ◽  
Dynamic Regime ◽  
The Body ◽  
Molecular Function ◽  
Frequency Range ◽  
Peripheral Tissues ◽  
Peripheral Clock ◽  
Peripheral Clocks ◽  
Central Pacemaker ◽  
Peripheral Cells

Circadian rhythmicity in mammals is primarily driven by the suprachiasmatic nucleus (SCN), often called the central pacemaker, which converts the photic information of light and dark cycles into neuronal and hormonal signals in the periphery of the body. Cells of peripheral tissues respond to these centrally mediated cues by adjusting their molecular function to optimize organism performance. Numerous systemic cues orchestrate peripheral rhythmicity, such as feeding, body temperature, the autonomic nervous system, and hormones. We propose a semimechanistic model for the entrainment of peripheral clock genes by cortisol as a representative entrainer of peripheral cells. This model demonstrates the importance of entrainer's characteristics in terms of the synchronization and entrainment of peripheral clock genes, and predicts the loss of intercellular synchrony when cortisol moves out of its homeostatic amplitude and frequency range, as has been observed clinically in chronic stress and cancer. The model also predicts a dynamic regime of entrainment, when cortisol has a slightly decreased amplitude rhythm, where individual clock genes remain relatively synchronized among themselves but are phase shifted in relation to the entrainer. The model illustrates how the loss of communication between the SCN and peripheral tissues could result in desynchronization of peripheral clocks.

scholarly journals Roles of Neuropeptides, VIP and AVP, in the Mammalian Central Circadian Clock

2021 ◽  
Vol 15 ◽  
Author(s):  
Daisuke Ono ◽  
Ken-ichi Honma ◽  
Sato Honma
Keyword(s):  
Transcription Factors ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Cellular Networks ◽  
Clock Genes ◽  
Circadian System ◽  
Developmental Changes ◽  
Circadian Period ◽  
Functional Roles ◽  
Environmental Light

In mammals, the central circadian clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Individual SCN cells exhibit intrinsic oscillations, and their circadian period and robustness are different cell by cell in the absence of cellular coupling, indicating that cellular coupling is important for coherent circadian rhythms in the SCN. Several neuropeptides such as arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) are expressed in the SCN, where these neuropeptides function as synchronizers and are important for entrainment to environmental light and for determining the circadian period. These neuropeptides are also related to developmental changes of the circadian system of the SCN. Transcription factors are required for the formation of neuropeptide-related neuronal networks. Although VIP is critical for synchrony of circadian rhythms in the neonatal SCN, it is not required for synchrony in the embryonic SCN. During postnatal development, the clock genes cryptochrome (Cry)1 and Cry2 are involved in the maturation of cellular networks, and AVP is involved in SCN networks. This mini-review focuses on the functional roles of neuropeptides in the SCN based on recent findings in the literature.

scholarly journals Diurnal Rhythmicity of the Clock Genes Per1 and Per2 in the Rat Ovary

Endocrinology ◽  
2006 ◽  
Vol 147 (8) ◽  
pp. 3769-3776 ◽  
Author(s):  
Jan Fahrenkrug ◽  
Birgitte Georg ◽  
Jens Hannibal ◽  
Peter Hindersson ◽  
Søren Gräs
Keyword(s):  
In Situ Hybridization ◽  
Circadian Clock ◽  
Estrous Cycle ◽  
Clock Genes ◽  
Continuous Darkness ◽  
Peripheral Tissues ◽  
Hybridization Histochemistry ◽  
In Situ Hybridization Histochemistry ◽  
Rat Ovary

Circadian rhythms are generated by endogenous clocks in the central brain oscillator, the suprachiasmatic nucleus, and peripheral tissues. The molecular basis for the circadian clock consists of a number of genes and proteins that form transcriptional/translational feedback loops. In the mammalian gonads, clock genes have been reported in the testes, but the expression pattern is developmental rather than circadian. Here we investigated the daily expression of the two core clock genes, Per1 and Per2, in the rat ovary using real-time RT-PCR, in situ hybridization histochemistry, and immunohistochemistry. Both Per1 and Per2 mRNA displayed a statistically significant rhythmic oscillation in the ovary with a period of 24 h in: 1) a group of rats during proestrus and estrus under 12-h light,12-h dark cycles; 2) a second group of rats representing a mixture of all 4 d of the estrous cycle under 12-h light,12-h dark conditions; and 3) a third group of rats representing a mixture of all 4 d of estrous cycle during continuous darkness. Per1 mRNA was low at Zeitgeber time 0–2 and peaked at Zeitgeber time 12–14, whereas Per2 mRNA was delayed by approximately 4 h relative to Per1. By in situ hybridization histochemistry, Per mRNAs were localized to steroidogenic cells in preantral, antral, and preovulatory follicles; corpora lutea; and interstitial glandular tissue. With newly developed antisera, we substantiated the expression of Per1 and Per2 in these cells by single/double immunohistochemistry. Furthermore, we visualized the temporal intracellular movements of PER1 and PER2 proteins. These findings suggest the existence of an ovarian circadian clock, which may play a role both locally and in the hypothalamo-pituitary-ovarian axis.

scholarly journals Effects of resveratrol on changes induced by high-fat feeding on clock genes in rats

2013 ◽  
Vol 110 (8) ◽  
pp. 1421-1428 ◽  
Author(s):  
Jonatan Miranda ◽  
María P. Portillo ◽  
Juan Antonio Madrid ◽  
Noemí Arias ◽  
M. Terasa Macarulla ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Protein Expression ◽  
Fatty Acid Synthase ◽  
Clock Genes ◽  
The Body ◽  
Control Group ◽  
Standard Diet ◽  
High Fat ◽  
Peripheral Tissues ◽  
Fat Feeding

In mammals, the main component of the circadian system is the suprachiasmatic nucleus in the hypothalamus. However, circadian clocks are also present in most peripheral tissues, such as adipose tissue. The aim of the present study was to analyse the potential effects of resveratrol on changes induced by high-fat feeding in the expression of clock genes and clock-controlled genes in the white adipose tissue from rats. For this purpose, rats were divided into three groups: a control group, fed a standard diet, and two other groups, either fed a high-fat diet supplemented with resveratrol (RSV) or no resveratrol (HF). The expression of clock genes and clock-controlled genes was analysed by RT-PCR. Protein expression and fatty acid synthase (FAS) activity were also analysed. When comparing the controls, the RSV group showed similar patterns of response to the HF group, except for reverse erythroblastosis virus α (Rev-Erbα), which was down-regulated. The expression of this gene reached the same levels as in control rats. The response pattern of protein expression forRev-Erbαwas similar to that found for gene expression. High-fat feeding up-regulated all adipogenic genes and resveratrol did not modify them. In the HF group, the activity of FAS tended to increase, while resveratrol decreased. In conclusion, resveratrol reverses the change induced by high-fat feeding in the expression ofRev-Erbαin adipose tissue, which means that clock machinery is a target for this polyphenol. This change seems to be related to reduced lipogenesis, which might be involved in the body fat-lowering effect of this molecule.

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