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Disturbances of Circadian Hormonal and Metabolic Rhythms in a Changing Environment

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 28471

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Special Issue Editor

Prof. Dr. Michal Zeman

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Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia
Interests: biological rhythms; sleep disorders; chronobiology; physiology; melatonin; testosterone; circadian rhythms; endocrinology
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Special Issue Information

Dear Colleagues,

The neuroendocrine system plays a key role in adaptations of animals and humans to variations of environmental conditions. The system is under complex feedback control, and the production of most hormones exhibits distinct circadian rhythms. Circadian oscillations are generated at the molecular level by coordinated transcription of clock genes and synchronize many physiological and metabolic processes. Entrained circadian rhythms in the neuroendocrine system enable animals and humans to cope effectively with environmental challenges and orchestrate metabolic efficiency at the level of organs, cells, and molecular pathways. Circadian rhythms are entrained by environmental cycles, such as the light–dark cycle, temperature, and food availability, which are recently disturbed by light pollution, warming of environment, and increasing unpredictability of external environmental conditions. Moreover, in humans, there has been a significant change in lifestyles because of shift work, exposure to unnatural light in an impropriate phase of the day, sedentary behaviors, high caloric diets, and shifting of physical activity and food intake out of phase with environment cycles. These changes can contribute to the recent burden of civilization diseases and decreasing biodiversity. Understanding the molecular mechanisms at the interface between the circadian and neuroendocrine system and their control of metabolic processes can help to identify the key nodes, which are important for health. Both systems are coupled especially at the level of the hypothalamus because the master circadian oscillator localized in the suprachiasmatic nuclei is tightly connected with the nuclei controlling the synthesis and release of neurohormones, liberins, and statins, which coordinate different hormonal axes regulating all vital functions. Therefore, disturbances in the coordinated activity of both systems and their response to changing environment can explain, at least partly, the negative consequences of recent less predictable environmental conditions on health and biodiversity.

This Special Issue will focus on molecular mechanisms underlying rhythms in the biosynthesis and action of different hormones, which are disturbed by recently changing environmental conditions such as light pollution, stress, metabolic dysfunction, and diseases. Special emphasis is given on metabolic rhythms, which are not only outputs of the circadian system but also feedback to the circadian clocks to align tissue-specific processes with environmental conditions.

Prof. Dr. Michal Zeman
Guest Editor

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Keywords

neuroendocrine system
metabolic rhythms
hormonal rhythms
circadian system
environmental factors
metabolic dysfunction

Published Papers (7 papers)

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Research

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15 pages, 2490 KiB

Open AccessArticle

Artificial Dim Light at Night during Pregnancy Can Affect Hormonal and Metabolic Rhythms in Rat Offspring

by Zuzana Dzirbíková, Katarína Stebelová, Katarína Kováčová, Monika Okuliarová, Lucia Olexová and Michal Zeman

Int. J. Mol. Sci. 2022, 23(23), 14544; https://doi.org/10.3390/ijms232314544 - 22 Nov 2022

Cited by 7 | Viewed by 1598

Abstract

Artificial light at night (ALAN) is considered an environmental risk factor that can interfere with the circadian control of the endocrine system and metabolism. We studied the impact of ALAN during pregnancy on the hormonal and biochemical parameters in rat pups at postnatal (P) days P3, P10, and P20. Control dams (CTRL) were kept in a standard light-dark regime, and ALAN dams were exposed to dim ALAN (<2 lx) during the whole pregnancy. A plasma melatonin rhythm was found in all CTRL groups, whereas in ALAN pups, melatonin was not rhythmic at P3, and its amplitude was lowered at P10; no differences were found between groups at P20. Plasma corticosterone was rhythmic at P20 in both groups, with decreased mesor in ALAN pups. Plasma thyroid hormones exhibited an inconsistent developmental pattern, and vasopressin levels were suppressed at the beginning of the dark phase at P20 in ALAN compared to CTRL. Glucose and cholesterol showed significant daily rhythms in CTRL but not in ALAN offspring at P3. Exposure to ALAN during pregnancy disturbed the development of daily rhythms in measured hormones and metabolites, suggesting that ALAN during pregnancy can act as an endocrine disruptor that can interfere with the normal development of the progeny. Full article

(This article belongs to the Special Issue Disturbances of Circadian Hormonal and Metabolic Rhythms in a Changing Environment)

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11 pages, 1813 KiB

Open AccessArticle

Transcriptional Response of Circadian Clock Genes to an ‘Artificial Light at Night’ Pulse in the Cricket Gryllus bimaculatus

by Keren Levy, Bettina Fishman, Anat Barnea, Amir Ayali and Eran Tauber

Int. J. Mol. Sci. 2022, 23(19), 11358; https://doi.org/10.3390/ijms231911358 - 26 Sep 2022

Cited by 7 | Viewed by 2655

Abstract

Light is the major signal entraining the circadian clock that regulates physiological and behavioral rhythms in most organisms, including insects. Artificial light at night (ALAN) disrupts the natural light–dark cycle and negatively impacts animals at various levels. We simulated ALAN using dim light stimuli and tested their impact on gene expression in the cricket Gryllus bimaculatus, a model of insect physiology and chronobiology. At night, adult light–dark-regime-raised crickets were exposed for 30 min to a light pulse of 2–40 lx. The relative expression of five circadian-clock-associated genes was compared using qPCR. A dim ALAN pulse elicited tissue-dependent differential expression in some of these genes. The strongest effect was observed in the brain and in the optic lobe, the cricket’s circadian pacemaker. The expression of opsin-Long Wave (opLW) was upregulated, as well as cryptochrome1-2 (cry) and period (per). Our findings demonstrate that even a dim ALAN exposure may affect insects at the molecular level, underscoring the impact of ALAN on the circadian clock system. Full article

(This article belongs to the Special Issue Disturbances of Circadian Hormonal and Metabolic Rhythms in a Changing Environment)

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27 pages, 12098 KiB

Open AccessArticle

Morphofunctional State and Circadian Rhythms of the Liver of Female Rats under the Influence of Chronic Alcohol Intoxication and Constant Lighting

by David A. Areshidze and Maria A. Kozlova

Int. J. Mol. Sci. 2022, 23(18), 10744; https://doi.org/10.3390/ijms231810744 - 15 Sep 2022

Cited by 2 | Viewed by 1628

Abstract

A separate and combined effect of constant illumination and chronic alcohol intoxication (CAI) on diurnal dynamics of micromorphometric parameters of hepatocytes in female Wistar rats and p53, Ki-67, PER2, BMAL1, and ADH5 expression in these cells were studied. The increase in apoptotic activity and proliferation in all animals under the action of chronodestructors is shown. All experimental animals showed a decrease in BMAL1 expression and increase in PER2 expression; ADH5 is overexpressed under the influence of ethanol. Circadian rhythms (CRs) of BMAL1, PER2, p53, and Ki-67 expression persist in all groups, except combined action of chronodestructors, and ADH5 CRs persist in all groups—thus, these rhythms in females are quite stable. CRs of the hepatocyte nuclei area are preserved in all the studied groups, although they undergo a significant shift. At the same time, the CRs of the hepatocyte area are destroyed under the action of light, both independently and in combination with CAI, and the CR of the nuclear-cytoplasmic ratio (NCR) is destroyed by exposure to CAI. It can be assumed that CRs of the hepatocyte area are significantly affected by dark deprivation and NCR rhythm is sensitive to ethanol consumption, while the stability of studied genes’ expression rhythms at separate influences of studied chronodestructors is maintained by yet unknown adaptation mechanisms. It is necessary to note that, according to our previous studies of male rats, rat females show significantly greater stability of the studied CRs. Full article

(This article belongs to the Special Issue Disturbances of Circadian Hormonal and Metabolic Rhythms in a Changing Environment)

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Review

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15 pages, 645 KiB

Open AccessReview

Disturbances of Hormonal Circadian Rhythms by Light Pollution

by Michal Zeman, Monika Okuliarova and Valentina Sophia Rumanova

Int. J. Mol. Sci. 2023, 24(8), 7255; https://doi.org/10.3390/ijms24087255 - 14 Apr 2023

Cited by 3 | Viewed by 2426

Abstract

The circadian rhythms evolved to anticipate and cope with cyclic changes in environmental conditions. This adaptive function is currently compromised by increasing levels of artificial light at night (ALAN), which can represent a risk for the development of diseases of civilisation. The causal links are not completely understood, and this featured review focuses on the chronodisruption of the neuroendocrine control of physiology and behaviour by dim ALAN. The published data indicate that low levels of ALAN (2–5 lux) can attenuate the molecular mechanisms generating circadian rhythms in the central oscillator, eliminate the rhythmic changes in dominant hormonal signals, such as melatonin, testosterone and vasopressin, and interfere with the circadian rhythm of the dominant glucocorticoid corticosterone in rodents. These changes are associated with a disturbed daily pattern of metabolic changes and behavioural rhythms in activity and food and water intake. The increasing levels of ALAN require the identification of the pathways mediating possible negative consequences on health to design effective mitigation strategies to eliminate or minimise the effects of light pollution. Full article

(This article belongs to the Special Issue Disturbances of Circadian Hormonal and Metabolic Rhythms in a Changing Environment)

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25 pages, 803 KiB

Open AccessReview

Circadian Rhythms Disrupted by Light at Night and Mistimed Food Intake Alter Hormonal Rhythms and Metabolism

by O. Hecmarie Meléndez-Fernández, Jennifer A. Liu and Randy J. Nelson

Int. J. Mol. Sci. 2023, 24(4), 3392; https://doi.org/10.3390/ijms24043392 - 08 Feb 2023

Cited by 26 | Viewed by 11867

Abstract

Availability of artificial light and light-emitting devices have altered human temporal life, allowing 24-hour healthcare, commerce and production, and expanding social life around the clock. However, physiology and behavior that evolved in the context of 24 h solar days are frequently perturbed by exposure to artificial light at night. This is particularly salient in the context of circadian rhythms, the result of endogenous biological clocks with a rhythm of ~24 h. Circadian rhythms govern the temporal features of physiology and behavior, and are set to precisely 24 h primarily by exposure to light during the solar day, though other factors, such as the timing of meals, can also affect circadian rhythms. Circadian rhythms are significantly affected by night shift work because of exposure to nocturnal light, electronic devices, and shifts in the timing of meals. Night shift workers are at increased risk for metabolic disorder, as well as several types of cancer. Others who are exposed to artificial light at night or late mealtimes also show disrupted circadian rhythms and increased metabolic and cardiac disorders. It is imperative to understand how disrupted circadian rhythms alter metabolic function to develop strategies to mitigate their negative effects. In this review, we provide an introduction to circadian rhythms, physiological regulation of homeostasis by the suprachiasmatic nucleus (SCN), and SCN-mediated hormones that display circadian rhythms, including melatonin and glucocorticoids. Next, we discuss circadian-gated physiological processes including sleep and food intake, followed by types of disrupted circadian rhythms and how modern lighting disrupts molecular clock rhythms. Lastly, we identify how disruptions to hormones and metabolism can increase susceptibility to metabolic syndrome and risk for cardiovascular diseases, and discuss various strategies to mitigate the harmful consequences associated with disrupted circadian rhythms on human health. Full article

(This article belongs to the Special Issue Disturbances of Circadian Hormonal and Metabolic Rhythms in a Changing Environment)

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23 pages, 838 KiB

Open AccessReview

Circadian Disruption and Consequences on Innate Immunity and Inflammatory Response

by Viera Jerigova, Michal Zeman and Monika Okuliarova

Int. J. Mol. Sci. 2022, 23(22), 13722; https://doi.org/10.3390/ijms232213722 - 08 Nov 2022

Cited by 11 | Viewed by 2871

Abstract

Circadian rhythms control almost all aspects of physiology and behavior, allowing temporal synchrony of these processes between each other, as well as with the external environment. In the immune system, daily rhythms of leukocyte functions can determine the strength of the immune response, thereby regulating the efficiency of defense mechanisms to cope with infections or tissue injury. The natural light/dark cycle is the prominent synchronizing agent perceived by the circadian clock, but this role of light is highly compromised by irregular working schedules and unintentional exposure to artificial light at night (ALAN). The primary concern is disrupted circadian control of important physiological processes, underlying potential links to adverse health effects. Here, we first discuss the immune consequences of genetic circadian disruption induced by mutation or deletion of specific clock genes. Next, we evaluate experimental research into the effects of disruptive light/dark regimes, particularly light-phase shifts, dim ALAN, and constant light on the innate immune mechanisms under steady state and acute inflammation, and in the pathogenesis of common lifestyle diseases. We suggest that a better understanding of the mechanisms by which circadian disruption influences immune status can be of importance in the search for strategies to minimize the negative consequences of chronodisruption on health. Full article

(This article belongs to the Special Issue Disturbances of Circadian Hormonal and Metabolic Rhythms in a Changing Environment)

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20 pages, 2918 KiB

Open AccessReview

Role of Circadian Transcription Factor Rev-Erb in Metabolism and Tissue Fibrosis

by Ghulam Shere Raza, Nalini Sodum, Yagmur Kaya and Karl-Heinz Herzig

Int. J. Mol. Sci. 2022, 23(21), 12954; https://doi.org/10.3390/ijms232112954 - 26 Oct 2022

Cited by 9 | Viewed by 4004

Abstract

Circadian rhythms significantly affect metabolism, and their disruption leads to cardiometabolic diseases and fibrosis. The clock repressor Rev-Erb is mainly expressed in the liver, heart, lung, adipose tissue, skeletal muscles, and brain, recognized as a master regulator of metabolism, mitochondrial biogenesis, inflammatory response, and fibrosis. Fibrosis is the response of the body to injuries and chronic inflammation with the accumulation of extracellular matrix in tissues. Activation of myofibroblasts is a key factor in the development of organ fibrosis, initiated by hormones, growth factors, inflammatory cytokines, and mechanical stress. This review summarizes the importance of Rev-Erb in ECM remodeling and tissue fibrosis. In the heart, Rev-Erb activation has been shown to alleviate hypertrophy and increase exercise capacity. In the lung, Rev-Erb agonist reduced pulmonary fibrosis by suppressing fibroblast differentiation. In the liver, Rev-Erb inhibited inflammation and fibrosis by diminishing NF-κB activity. In adipose tissue, Rev- Erb agonists reduced fat mass. In summary, the results of multiple studies in preclinical models demonstrate that Rev-Erb is an attractive target for positively influencing dysregulated metabolism, inflammation, and fibrosis, but more specific tools and studies would be needed to increase the information base for the therapeutic potential of these substances interfering with the molecular clock. Full article

(This article belongs to the Special Issue Disturbances of Circadian Hormonal and Metabolic Rhythms in a Changing Environment)

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