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- Effect of circadian rhythm desynchronization on gluconeogenic enzyme protein in rat livers. (A) Western blot quantitative analysis showing increased PEPCK protein in desynchronized (DSC) rats. (B) Representative blots of proteins. GAPDH content was used as control loading. Results are expressed as relative (%) to the control group and as M ± s.e.m. (n = 6). *P < 0.05 indicates a significant difference from CTR rats according to an unpaired Student’s t test.
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Disruptions in circadian rhythms have been associated with several diseases, including cardiovascular and metabolic disorders. Forced internal desynchronization induced by a period of T-cycles of 22-h (T22 protocol) reaches the lower limit of entrainment and dissociates the circadian rhythmicity of the locomotor activity into two components, driven...
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... Overall, these studies show the role of MT in the restoration of the oxidative status in adipose tissue from obese animals. There are much fewer studies on the desynchronization of the circadian rhythm; however, a very comprehensive research study on the effects of forced internal desynchronization induced by a period of T-cycles of 22 h of male Wistar rats showed a significant decrease in HDL-cholesterol, a raise in LDL-cholesterol, a decrease in SOD and CAT protein expression and a reduction in baroreflex sensitivity [99]. This experiment indicates that cardio-metabolic impairment can be reproduced in rats and, indirectly confirms the experiments described above. ...
Metabolic syndrome has been associated in many studies with working in shifts. Even if the mechanistic details are not fully understood, forced sleep deprivation and exposure to light, as happens during night shifts, or irregular schedules with late or very early onset of the working program, lead to a sleep–wake rhythm misalignment, metabolic dysregulation and oxidative stress. The cyclic melatonin secretion is regulated by the hypothalamic suprachiasmatic nuclei and light exposure. At a central level, melatonin promotes sleep and inhibits wake-signals. Beside this role, melatonin acts as an antioxidant and influences the functionality of the cardiovascular system and of different metabolic processes. This review presents data about the influence of night shifts on melatonin secretion and oxidative stress. Assembling data from epidemiological, experimental and clinical studies contributes to a better understanding of the pathological links between chronodisruption and the metabolic syndrome related to working in shifts.
... Disturbances of daily rhythmicity have been related to cardiovascular disease, diabetes, aging, and obesity (Sohail et al., 2015;Sletten et al., 2020). When rodents are under forced desynchrony (modeling circadian disruption), glucose metabolism and insulin sensitivity become impaired (Karatsoreos et al., 2011;de Oliveira et al., 2019). However, the precise mechanisms linking circadian disruption with adverse metabolic consequences are not fully understood. ...
Industrialization has greatly changed human lifestyle; work and leisure activities have been moved indoors, and artificial light has been used to illuminate the night. As cyclic environmental cues such as light and feeding become weak and/or irregular, endogenous circadian systems are increasingly being disrupted. These disruptions are associated with metabolic dysfunction, possibly contributing to increased rates of overweight and obesity worldwide. Here, we aimed to investigate how activity-rest rhythms, patterns of light exposure, and levels of urbanization may be associated with body mass index (BMI) in a sample of rural and urban Quilombola communities in southern Brazil. These are characterized as remaining social groups who resisted the slavery regime that prevailed in Brazil. Quilombola communities were classified into five groups according to their stage of urbanization: from rural areas with no access to electricity to highly urbanized communities. We collected anthropometric data to calculate BMI, which was categorized as follows: from ≥ 18.5 kg/m² to < 25 kg/m² = normal weight; from ≥ 25 kg/m² to < 30 kg/m² = overweight; and ≥ 30 kg/m² = obese. Subjects were asked about their sleep routines and light exposure on workdays and work-free days using the Munich Chronotype Questionnaire (N = 244 included). In addition, we analyzed actimetry data from 121 participants with seven consecutive days of recordings. Living in more urbanized areas and higher intradaily variability (IV) of activity-rest rhythms were associated with an increased risk of belonging to the overweight or obese group, when controlling for age and sex. These findings are consistent with preclinical data and point to potential strategies in obesity prevention and promotion of healthy metabolic profiles.
... A redução na qualidade e quantidade do sono estão associadas às queixas generalizadas de fadiga, ansiedade, depressão e aumento do neuroticismo 29 . Bem como, evidências crescentes de efeitos cardiovasculares adversos e possível aumento de distúrbios metabólicos relacionados [30][31][32] . ...
Os profissionais da saúde estão sujeitos a trabalhos em turnos em horários não convencionais, o que muitas vezes, pode não coincidir com seus ritmos circadianos endógenos. Neste estudo, o objetivo foi investigar de qual modo a preferência diurna associa-se com os padrões do ciclo sono e vigília, em especial a qualidade do sono e da sonolência diurna excessiva. Para isso, foram aplicados questionários específicos para descrever os turnos de trabalho e para avaliar os parâmetros de sono. Utilizamos o questionário de Pittsburgh para avaliar a qualidade de sono, o de Epworth para avaliar a sonolência diurna e o HO para a preferência diurna. Os testes t de Student, de correlação de Pearson e de Análise de variância (ANOVA) foram utilizados a fim de analisar os parâmetros de sono dos trabalhadores em turnos de hospitais. A amostra constituiu-se de 59 indivíduos, de ambos os sexos, que trabalhavam no regime 12h de trabalho intercalados com 36h de folga em turnos diurnos ou noturnos. Verificamos que (i) a preferência diurna individual não é levada em conta na atribuição do turno; (ii) trabalhadores de ambos os turnos apresentam má qualidade de sono e (iii) queixas de sonolência diurna semelhantes. Entretanto, encontramos correlação entre a má qualidade de sono e a sonolência diurna excessiva somente entre os trabalhadores noturnos
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Clock genes work as an auto-regulated transcription-translational loop of circadian genes that drives the circadian rhythms in each cell and they are essential to physiological requests. Since metabolism is a dynamic process, it involves several physiological variables that circadian cycling. The clock genes alterations can affect multiple systems concomitantly, because they constitute the promoter factors for relevant metabolic pathways. Considering the intertwined structure of signaling, regulatory, and metabolic processes within a cell, we employed a genome-scale biomolecular network. Accordingly, a meta-analysis of diabetic-associated transcriptomic datasets was performed, and the core information on differentially expressed genes (DEGs) was obtained by statistical analyses. In the current study, meta-analysis was performed on type 2 diabetes, circadian rhythm-related genes, and breast, bladder, liver, pancreas, colon and rectum cancer-associated transcriptome data using the integration of gene expression profiles with genome-scale biomolecular networks in diabetes samples. First, we detected downregulated and upregulated DEGs in mouse cortex and hypothalamus samples of mice with sleep deprivation. In summary, upregulated genes active genes associated with oxidative phosphorylation, cancer and diabetes, mainly in hypothalamus specimens. In cortex, we observed mainly downregulation of immune system. DEGs were combined with 214 circadian rhythm related genes to type 2 DM and cancer samples. We observed that several common genes deregulated in both diseases. Klf10, Ntkr3, Igf1, Usp2, Ezh2 were both downregulated in type 2 DM and cancer samples, while Arntl2 and Agrp were upregulated. It seems that the changes in mRNA are contributing to the phenotypic changes in type 2 DM, resulting in phenotypic changes associated with the malignant transformation. Taking those genes to perform a survival analysis, we found only Igf1, Usp2 and Arntl2 genes associated with patient outcomes. While Igf1 and Usp2 downregulation had a negative impact, Arntl2 upregulation was associated with poor survival both in BLCA and BRCA cancer samples. Our data stimulate efforts in news studies to achieve the experimental and clinical validation about these biomolecules.
... In mammals, light information is perceived by the retina and transmitted to the suprachiasmatic nuclei through the retinohypothalamic tract. The projections of the suprachiasmatic nuclei, have at least four neuronal targets: endocrine neurons, autonomic neurons of the paraventricular nucleus of the hypothalamus, other hypothalamic structures, and areas outside the hypothalamus (Bozek et al., 2009;de Oliveira et al., 2019). These efferent pathways are able to synchronize peripheral clocks, controlling various physiological functions, such as hormone releasing, food behavior and temperature fluctuations. ...
The circadian timing system controls glucose metabolism in a time‐of‐day dependent manner. In mammals, the circadian timing system consists of the main central clock in the bilateral suprachiasmatic nucleus (SCN) of the anterior hypothalamus and subordinate clocks in peripheral tissues. The oscillations produced by these different clocks with a period of approximately 24‐h are generated by the transcriptional‐translational feedback loops of a set of core clock genes. Glucose homeostasis is one of the daily rhythms controlled by this circadian timing system. The central pacemaker in the SCN controls glucose homeostasis through its neural projections to hypothalamic hubs that are in control of feeding behavior and energy metabolism. Using hormones such as adrenal glucocorticoids and melatonin and the autonomic nervous system, the SCN modulates critical processes such as glucose production and insulin sensitivity. Peripheral clocks in tissues, such as the liver, muscle, and adipose tissue serve to enhance and sustain these SCN signals. In the optimal situation all these clocks are synchronized and aligned with behavior and the environmental light/dark cycle. A negative impact on glucose metabolism becomes apparent when the internal timing system becomes disturbed, also known as circadian desynchrony or circadian misalignment. Circadian desynchrony may occur at several levels, as the mistiming of light exposure or sleep will especially affect the central clock, whereas mistiming of food intake or physical activity will especially involve the peripheral clocks. In this review, we will summarize the literature investigating the impact of circadian desynchrony on glucose metabolism and how it may result in the development of insulin resistance. In addition, we will discuss potential strategies aimed at reinstating circadian synchrony to improve insulin sensitivity and contribute to the prevention of type 2 diabetes.
Poor sleep standards are common in everyday life; it is frequently linked to a rise in stress levels. The adrenal gland interacts physiologically with the pineal gland in the stress response. Pineal gland is a small endocrine organ that modulates sleep patterns. This work aimed to evaluate the inverted light–dark cycle rhythm on the histological changes within the adrenal cortex and pineal gland in adult male albino rats. Twenty adult male albino rats were equally divided into two groups: For the first control group, animals were kept on daylight–darkness for 12–12 h. The second group was kept under an inverted 12- to 12-h light–darkness cycle for 4 weeks. Adrenal sections were subjected to biochemical, histological, and immunohistochemical study. Inverted light–dark cycle group recorded a significant elevation of plasma corticosterone, tissue malondialdehyde, tumor necrosis factor-α, and interleukin-1β (IL-1β) associated with a significant reduction of catalase and superoxide dismutase. Adrenal cortex showed biochemical and histological changes. Pineal glands also showed loss of lobular architecture. A significant upregulation in activated inducible nitric oxide synthase (iNOS) and B-cell lymphoma-associated X (Bax) immunohistochemical expression was recorded in adrenal cortex associating with downregulation in B-cell lymphoma 2 (Bcl-2). It could be concluded that subchronic inverted light–dark cycle exerted direct effects on adrenal cortex and the pineal glands.
A network of cellular timers ensures the maintenance of homeostasis by temporal modulation of physiological processes across the day. These so-called circadian clocks are synchronized to geophysical time by external time cues (or zeitgeber s). In modern societies, natural environmental cycles are disrupted by artificial lighting, around-the-clock availability of food or shift work. Such contradictory zeitgeber input promotes chronodisruption, i.e. , the perturbation of internal circadian rhythms, resulting in adverse health outcomes. While this phenomenon is well described, it is still poorly understood at which level of organization perturbed rhythms impact on health and wellbeing. In this review, we discuss different levels of chronodisruption and what is known about their health effects. We summarize the results of disrupted phase coherence between external and internal time vs. misalignment of tissue clocks amongst each other, i.e., internal desynchrony. Last, phase incoherence can also occur at the tissue level itself. Here, alterations in phase coordination can emerge between cellular clocks of the same tissue or between different clock genes within the single cell. A better understanding of the mechanisms of circadian misalignment and its effects on physiology will help to find effective tools to prevent or treat disorders arising from modern-day chronodisruptive environments.
A network of cellular timers ensures the maintenance of homeostasis by temporal modulation of physiological processes across the day. These so-called circadian clocks are synchronized to geophysical time by external time cues (or zeitgeber s). In modern societies, natural environmental cycles are disrupted by artificial lighting, around-the-clock availability of food or shiftwork. Such contradictory zeitgeber input promotes chronodisruption, i.e. , the perturbation of internal circadian rhythms, resulting in adverse health outcomes. While this phenomenon is well described, it is still poorly understood at which level of organization perturbed rhythms impact on health and wellbeing. In this review, we discuss different levels of chronodisruption and what is known about their health effects. We summarize the results of disrupted phase coherence between external and internal time vs. misalignment of tissue clocks amongst each other, i.e., internal desynchrony. Last, phase incoherence can also occur at the tissue level itself. Here, alterations in phase coordination can emerge between cellular clocks of the same tissue or between different clock genes within the single cell. A better understanding of the mechanisms of circadian misalignment and its effects on physiology will help to find effective tools to prevent or treat disorders arising from modern-day chronodisruptive environments.
