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12 pages, 1356 KiB

Open AccessArticle

Light Exposure, Physical Activity, and Indigeneity Modulate Seasonal Variation in NR1D1 (REV-ERBα) Expression

by Denis Gubin, Sergey Kolomeichuk, Konstantin Danilenko, Oliver Stefani, Alexander Markov, Ivan Petrov, Kirill Voronin, Marina Mezhakova, Mikhail Borisenkov, Aislu Shigabaeva, Julia Boldyreva, Julianna Petrova, Dietmar Weinert and Germaine Cornelissen

Biology 2025, 14(3), 231; https://doi.org/10.3390/biology14030231 - 25 Feb 2025

Viewed by 685

Abstract

Nuclear receptor subfamily 1 group D member 1 (NR1D1 or REV-ERBα) is a crucial element of the circadian clock’s transcriptional and translational feedback loop. Understanding its expression in humans is critical for elucidating its role in circadian rhythms and metabolic processes, and in [...] Read more.

Nuclear receptor subfamily 1 group D member 1 (NR1D1 or REV-ERBα) is a crucial element of the circadian clock’s transcriptional and translational feedback loop. Understanding its expression in humans is critical for elucidating its role in circadian rhythms and metabolic processes, and in finding potential links to various pathologies. In a longitudinal survey, we examined REV-ERBα expression at 08:00 using a real-time polymerase chain reaction (qRT-PCR) in blood mononuclear cells from Arctic native and non-native residents during equinoxes and solstices. REV-ERBα expression exhibited a pronounced seasonality, peaking at the summer solstice, and reaching a nadir at the winter solstice in both natives and non-natives, with a relatively higher summer peak in natives. After adjusting for age, sex, and body mass index, the amount and timing of light exposure, the amount of physical activity, and indigeneity emerged as significant predictors of REV-ERBα expression. Full article

(This article belongs to the Special Issue Biological Rhythms and Molecular Clockworks in Physiology and Pathology)

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17 pages, 6609 KiB

Open AccessArticle

Prolonged Sleep Deprivation Induces a Reprogramming of Circadian Rhythmicity with the Hepatic Metabolic Transcriptomic Profile

by Shiyan Liu, Kailin Zhuo, Yiming Wang, Xiaomei Wang and Yingying Zhao

Biology 2024, 13(7), 532; https://doi.org/10.3390/biology13070532 - 17 Jul 2024

Cited by 2 | Viewed by 2109

Abstract

Sleep disturbances can disrupt the overall circadian rhythm. However, the impact of sleep deprivation on the circadian rhythm of the liver and its underlying mechanisms still requires further exploration. In this study, we subjected male mice to 5 days of sleep deprivation and [...] Read more.

Sleep disturbances can disrupt the overall circadian rhythm. However, the impact of sleep deprivation on the circadian rhythm of the liver and its underlying mechanisms still requires further exploration. In this study, we subjected male mice to 5 days of sleep deprivation and performed liver transcriptome sequencing analysis at various time points within a 24-h period. Subsequently, we monitored the autonomic activity and food intake in these male mice for six days post-sleep deprivation. We observed alterations in sleep-wake and feeding rhythms in the first two days following sleep deprivation. Additionally, we also observed a decrease in 24-h serum-glucose levels. Liver transcriptome sequencing has shown that sleep deprivation induces the rhythmic transcription of a large number of genes, or alters the rhythmic properties of genes, which were then significantly enriched in the carbohydrate, lipid, and protein metabolism pathways. Our findings suggest that under conditions of prolonged sleep deprivation, the expression of metabolic-related genes in the liver was reset, leading to changes in the organism’s metabolic state to ensure energy supply to sustain prolonged wakefulness. Full article

(This article belongs to the Special Issue Biological Rhythms and Molecular Clockworks in Physiology and Pathology)

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21 pages, 3566 KiB

Open AccessArticle

Blue Light and Temperature Actigraphy Measures Predicting Metabolic Health Are Linked to Melatonin Receptor Polymorphism

by Denis Gubin, Konstantin Danilenko, Oliver Stefani, Sergey Kolomeichuk, Alexander Markov, Ivan Petrov, Kirill Voronin, Marina Mezhakova, Mikhail Borisenkov, Aislu Shigabaeva, Natalya Yuzhakova, Svetlana Lobkina, Dietmar Weinert and Germaine Cornelissen

Biology 2024, 13(1), 22; https://doi.org/10.3390/biology13010022 - 30 Dec 2023

Cited by 14 | Viewed by 4670

Abstract

This study explores the relationship between the light features of the Arctic spring equinox and circadian rhythms, sleep and metabolic health. Residents (N = 62) provided week-long actigraphy measures, including light exposure, which were related to body mass index (BMI), leptin and cortisol. [...] Read more.

This study explores the relationship between the light features of the Arctic spring equinox and circadian rhythms, sleep and metabolic health. Residents (N = 62) provided week-long actigraphy measures, including light exposure, which were related to body mass index (BMI), leptin and cortisol. Lower wrist temperature (wT) and higher evening blue light exposure (BLE), expressed as a novel index, the nocturnal excess index (NEIbl), were the most sensitive actigraphy measures associated with BMI. A higher BMI was linked to nocturnal BLE within distinct time windows. These associations were present specifically in carriers of the MTNR1B rs10830963 G-allele. A larger wake-after-sleep onset (WASO), smaller 24 h amplitude and earlier phase of the activity rhythm were associated with higher leptin. Higher cortisol was associated with an earlier M10 onset of BLE and with our other novel index, the Daylight Deficit Index of blue light, DDIbl. We also found sex-, age- and population-dependent differences in the parametric and non-parametric indices of BLE, wT and physical activity, while there were no differences in any sleep characteristics. Overall, this study determined sensitive actigraphy markers of light exposure and wT predictive of metabolic health and showed that these markers are linked to melatonin receptor polymorphism. Full article

(This article belongs to the Special Issue Biological Rhythms and Molecular Clockworks in Physiology and Pathology)

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20 pages, 3747 KiB

Open AccessArticle

Risk for Seasonal Affective Disorder (SAD) Linked to Circadian Clock Gene Variants

by Thanh Dang, William A. Russel, Tazmilur Saad, Luvna Dhawka, Ahmet Ay and Krista K. Ingram

Biology 2023, 12(12), 1532; https://doi.org/10.3390/biology12121532 - 15 Dec 2023

Cited by 3 | Viewed by 3541

Abstract

Molecular pathways affecting mood are associated with circadian clock gene variants and are influenced, in part, by the circadian clock, but the molecular mechanisms underlying this link are poorly understood. We use machine learning and statistical analyses to determine the circadian gene variants [...] Read more.

Molecular pathways affecting mood are associated with circadian clock gene variants and are influenced, in part, by the circadian clock, but the molecular mechanisms underlying this link are poorly understood. We use machine learning and statistical analyses to determine the circadian gene variants and clinical features most highly associated with symptoms of seasonality and seasonal affective disorder (SAD) in a deeply phenotyped population sample. We report sex-specific clock gene effects on seasonality and SAD symptoms; genotypic combinations of CLOCK3111/ZBTB20 and PER2/PER3B were significant genetic risk factors for males, and CRY2/PER3C and CRY2/PER3-VNTR were significant risk factors for females. Anxiety, eveningness, and increasing age were significant clinical risk factors for seasonality and SAD for females. Protective factors for SAD symptoms (in females only) included single gene variants: CRY1-GG and PER3-VNTR-4,5. Clock gene effects were partially or fully mediated by diurnal preference or chronotype, suggesting multiple indirect effects of clock genes on seasonality symptoms. Interestingly, protective effects of CRY1-GG, PER3-VNTR-4,5, and ZBTB20 genotypes on seasonality and depression were not mediated by chronotype, suggesting some clock variants have direct effects on depressive symptoms related to SAD. Our results support previous links between CRY2, PER2, and ZBTB20 genes and identify novel links for CLOCK and PER3 with symptoms of seasonality and SAD. Our findings reinforce the sex-specific nature of circadian clock influences on seasonality and SAD and underscore the multiple pathways by which clock variants affect downstream mood pathways via direct and indirect mechanisms. Full article

(This article belongs to the Special Issue Biological Rhythms and Molecular Clockworks in Physiology and Pathology)

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10 pages, 284 KiB

Open AccessArticle

Seasonal Pattern in Gestational Diabetes Mellitus in Poland: A Retrospective Cohort Study

by Marek J. Walkowiak, Małgorzata Jamka, Marcin Piotr Walkowiak, Paweł Gutaj and Ewa Wender-Ożegowska

Biology 2023, 12(11), 1376; https://doi.org/10.3390/biology12111376 - 27 Oct 2023

Viewed by 1535

Abstract

The existing literature does not address the question of the seasonal impact on pregnancy in Central-Eastern Europe; therefore, this study was designed to investigate the seasonal variation in gestational diabetes mellitus (GDM) based on a recent Polish sample. The data of 30,205 newborns [...] Read more.

The existing literature does not address the question of the seasonal impact on pregnancy in Central-Eastern Europe; therefore, this study was designed to investigate the seasonal variation in gestational diabetes mellitus (GDM) based on a recent Polish sample. The data of 30,205 newborns from singleton pregnancies and their mothers, including the date and gestational age of birth, neonatal sex and weight, maternal age and parity, mode of delivery, ethnicity, and a detailed list of comorbidities (including GDM), were retrospectively analysed. The prevalence of GDM was significantly (p < 0.0001) lower in spring (14.71%) than in the other seasons (16.78%). A higher incidence of GDM was observed for mothers who underwent an oral glucose tolerance test from June to August compared to those who were tested from December to February (17.34% vs. 14.75%, p < 0.0001). Similarly, there were significant differences between seasons with higher and lower insolation. The regression analysis revealed that seasonal patterns were significantly associated with the prevalence of GDM. In conclusion, this large retrospective cohort study demonstrated seasonal changes in GDM risk. The observed seasonal patterns may equally refer to mothers of babies born at term and prematurely. Further research concerning GDM risk and other seasonal and gender associations is warranted. Full article

(This article belongs to the Special Issue Biological Rhythms and Molecular Clockworks in Physiology and Pathology)

25 pages, 5481 KiB

Open AccessArticle

Transcriptomic Analysis of Light-Induced Genes in Nasonia vitripennis: Possible Implications for Circadian Light Entrainment Pathways

by Yifan Wang, Leo W. Beukeboom, Bregje Wertheim and Roelof A. Hut

Biology 2023, 12(9), 1215; https://doi.org/10.3390/biology12091215 - 6 Sep 2023

Cited by 1 | Viewed by 1939

Abstract

Circadian entrainment to the environmental day–night cycle is essential for the optimal use of environmental resources. In insects, opsin-based photoreception in the compound eye and ocelli and CRYPTOCHROME1 (CRY1) in circadian clock neurons are thought to be involved in sensing photic information, but [...] Read more.

Circadian entrainment to the environmental day–night cycle is essential for the optimal use of environmental resources. In insects, opsin-based photoreception in the compound eye and ocelli and CRYPTOCHROME1 (CRY1) in circadian clock neurons are thought to be involved in sensing photic information, but the genetic regulation of circadian light entrainment in species without light-sensitive CRY1 remains unclear. To elucidate a possible CRY1-independent light transduction cascade, we analyzed light-induced gene expression through RNA-sequencing in Nasonia vitripennis. Entrained wasps were subjected to a light pulse in the subjective night to reset the circadian clock, and light-induced changes in gene expression were characterized at four different time points in wasp heads. We used co-expression, functional annotation, and transcription factor binding motif analyses to gain insight into the molecular pathways in response to acute light stimulus and to form hypotheses about the circadian light-resetting pathway. Maximal gene induction was found after 2 h of light stimulation (1432 genes), and this included the opsin gene opblue and the core clock genes cry2 and npas2. Pathway and cluster analyses revealed light activation of glutamatergic and GABA-ergic neurotransmission, including CREB and AP-1 transcription pathway signaling. This suggests that circadian photic entrainment in Nasonia may require pathways that are similar to those in mammals. We propose a model for hymenopteran circadian light-resetting that involves opsin-based photoreception, glutamatergic neurotransmission, and gene induction of cry2 and npas2 to reset the circadian clock. Full article

(This article belongs to the Special Issue Biological Rhythms and Molecular Clockworks in Physiology and Pathology)

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Review

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20 pages, 1401 KiB

Open AccessReview

Role of the Circadian Gas-Responsive Hemeprotein NPAS2 in Physiology and Pathology

by Emanuele Murgo, Tommaso Colangelo, Maria Marina Bellet, Francesco Malatesta and Gianluigi Mazzoccoli

Biology 2023, 12(10), 1354; https://doi.org/10.3390/biology12101354 - 22 Oct 2023

Cited by 4 | Viewed by 3487

Abstract

Neuronal PAS domain protein 2 (NPAS2) is a hemeprotein comprising a basic helix–loop–helix domain (bHLH) and two heme-binding sites, the PAS-A and PAS-B domains. This protein acts as a pyridine nucleotide-dependent and gas-responsive CO-dependent transcription factor and is encoded by a gene whose [...] Read more.

Neuronal PAS domain protein 2 (NPAS2) is a hemeprotein comprising a basic helix–loop–helix domain (bHLH) and two heme-binding sites, the PAS-A and PAS-B domains. This protein acts as a pyridine nucleotide-dependent and gas-responsive CO-dependent transcription factor and is encoded by a gene whose expression fluctuates with circadian rhythmicity. NPAS2 is a core cog of the molecular clockwork and plays a regulatory role on metabolic pathways, is important for the function of the central nervous system in mammals, and is involved in carcinogenesis as well as in normal biological functions and processes, such as cardiovascular function and wound healing. We reviewed the scientific literature addressing the various facets of NPAS2 and framing this gene/protein in several and very different research and clinical fields. Full article

(This article belongs to the Special Issue Biological Rhythms and Molecular Clockworks in Physiology and Pathology)

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27 pages, 1018 KiB

Open AccessReview

Circadian Dysfunction in Adipose Tissue: Chronotherapy in Metabolic Diseases

by Erkan Civelek, Dilek Ozturk Civelek, Yasemin Kubra Akyel, Deniz Kaleli Durman and Alper Okyar

Biology 2023, 12(8), 1077; https://doi.org/10.3390/biology12081077 - 2 Aug 2023

Cited by 15 | Viewed by 4133

Abstract

Essential for survival and reproduction, the circadian timing system (CTS) regulates adaptation to cyclical changes such as the light/dark cycle, temperature change, and food availability. The regulation of energy homeostasis possesses rhythmic properties that correspond to constantly fluctuating needs for energy production and [...] Read more.

Essential for survival and reproduction, the circadian timing system (CTS) regulates adaptation to cyclical changes such as the light/dark cycle, temperature change, and food availability. The regulation of energy homeostasis possesses rhythmic properties that correspond to constantly fluctuating needs for energy production and consumption. Adipose tissue is mainly responsible for energy storage and, thus, operates as one of the principal components of energy homeostasis regulation. In accordance with its roles in energy homeostasis, alterations in adipose tissue’s physiological processes are associated with numerous pathologies, such as obesity and type 2 diabetes. These alterations also include changes in circadian rhythm. In the current review, we aim to summarize the current knowledge regarding the circadian rhythmicity of adipogenesis, lipolysis, adipokine secretion, browning, and non-shivering thermogenesis in adipose tissue and to evaluate possible links between those alterations and metabolic diseases. Based on this evaluation, potential therapeutic approaches, as well as clock genes as potential therapeutic targets, are also discussed in the context of chronotherapy. Full article

(This article belongs to the Special Issue Biological Rhythms and Molecular Clockworks in Physiology and Pathology)

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