The Liver in the Eyes of a Chronobiologist

Zwighaft, Ziv; Reinke, Hans; Asher, Gad

doi:10.1177/0748730416633552

Cited by 23 publications

(19 citation statements)

References 72 publications

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“…Clock function in the mammalian liver, particularly in relation to glucose homeostasis, has been well described ( [72,73]). In hepatocytes, the clock contributes to gluconeogenesis, glucose transport and lipid metabolism ( Fig.…”

Section: Molecular Clock Function In the Liver And Pancreas: Contribumentioning

confidence: 99%

Chronomedicine and type 2 diabetes: shining some light on melatonin

et al. 2016

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In mammals, the circadian timing system drives rhythms of physiology and behaviour, including the daily rhythms of feeding and activity. The timing system coordinates temporal variation in the biochemical landscape with changes in nutrient intake in order to optimise energy balance and maintain metabolic homeostasis. Circadian disruption (e.g. as a result of shift work or jet lag) can disturb this continuity and increase the risk of cardiometabolic disease. Obesity and metabolic disease can also disturb the timing and amplitude of the clock in multiple organ systems, further exacerbating disease progression. As our understanding of the synergy between the timing system and metabolism has grown, an interest has emerged in the development of novel clock-targeting pharmaceuticals or nutraceuticals for the treatment of metabolic dysfunction. Recently, the pineal hormone melatonin has received some attention as a potential chronotherapeutic drug for metabolic disease. Melatonin is well known for its sleep-promoting effects and putative activity as a chronobiotic drug, stimulating coordination of biochemical oscillations through targeting the internal timing system. Melatonin affects the insulin secretory activity of the pancreatic beta cell, hepatic glucose metabolism and insulin sensitivity. Individuals with type 2 diabetes mellitus have lower night-time serum melatonin levels and increased risk of comorbid sleep disturbances compared with healthy individuals. Further, reduced melatonin levels, and mutations and/or genetic polymorphisms of the melatonin receptors are associated with an increased risk of developing type 2 diabetes. Herein we review our understanding of molecular clock control of glucose homeostasis, detail the influence of circadian disruption on glucose metabolism in critical peripheral tissues, explore the contribution of melatonin signalling to the aetiology of type 2 diabetes, and discuss the pros and cons of melatonin chronopharmacotherapy in disease management.

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Section: Molecular Clock Function In the Liver And Pancreas: Contribumentioning

confidence: 99%

Chronomedicine and type 2 diabetes: shining some light on melatonin

et al. 2016

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“…Due to its numerous metabolic functions, the mouse liver is the most diurnally profiled organ [35]. Comparative studies between mouse datasets helped identify commonly expressed genes and their potential role in the circadian system [14].…”

Section: Resultsmentioning

confidence: 99%

Comparative Analysis of Vertebrate Diurnal/Circadian Transcriptomes

et al. 2017

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From photosynthetic bacteria to mammals, the circadian clock evolved to track diurnal rhythms and enable organisms to anticipate daily recurring changes such as temperature and light. It orchestrates a broad spectrum of physiology such as the sleep/wake and eating/fasting cycles. While we have made tremendous advances in our understanding of the molecular details of the circadian clock mechanism and how it is synchronized with the environment, we still have rudimentary knowledge regarding its connection to help regulate diurnal physiology. One potential reason is the sheer size of the output network. Diurnal/circadian transcriptomic studies are reporting that around 10% of the expressed genome is rhythmically controlled. Zebrafish is an important model system for the study of the core circadian mechanism in vertebrate. As Zebrafish share more than 70% of its genes with human, it could also be an additional model in addition to rodent for exploring the diurnal/circadian output with potential for translational relevance. Here we performed comparative diurnal/circadian transcriptome analysis with established mouse liver and other tissue datasets. First, by combining liver tissue sampling in a 48h time series, transcription profiling using oligonucleotide arrays and bioinformatics analysis, we profiled rhythmic transcripts and identified 2609 rhythmic genes. The comparative analysis revealed interesting features of the output network regarding number of rhythmic genes, proportion of tissue specific genes and the extent of transcription factor family expression. Undoubtedly, the Zebrafish model system will help identify new vertebrate outputs and their regulators and provides leads for further characterization of the diurnal cis-regulatory network.

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“…Metabolic syndrome and diabetes risk may be further increased by the timing of eating and food digestion being out of sync with peripheral oscillators in the liver [34] and gut [35]. Over the long run, physiological maladaptation to eating at abnormal circadian times is associated with developing metabolic syndrome (MetS) [36,37,38].…”

Section: Metabolic Healthmentioning

confidence: 99%

Shift Work: Disrupted Circadian Rhythms and Sleep—Implications for Health and Well-being

James

Honn

Gaddameedhi

et al. 2017

Curr Sleep Medicine Rep

293

217

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Purpose of review Our 24/7 society is dependent on shift work, despite mounting evidence for negative health outcomes from sleep displacement due to shift work. This paper reviews short- and long-term health consequences of sleep displacement and circadian misalignment due to shift work. Recent findings We focus on four broad health domains: metabolic health; risk of cancer; cardiovascular health; and mental health. Circadian misalignment affects these domains by inducing sleep deficiency, sympathovagal and hormonal imbalance, inflammation, impaired glucose metabolism, and dysregulated cell cycles. This leads to a range of medical conditions, including obesity, metabolic syndrome, type II diabetes, gastrointestinal dysfunction, compromised immune function, cardiovascular disease, excessive sleepiness, mood and social disorders, and increased cancer risk. Summary Interactions of biological disturbances with behavioral and societal factors shape the effects of shift work on health and well-being. Research is needed to better understand the underlying mechanisms and drive the development of countermeasures.

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The Liver in the Eyes of a Chronobiologist

Cited by 23 publications

References 72 publications

Chronomedicine and type 2 diabetes: shining some light on melatonin

Chronomedicine and type 2 diabetes: shining some light on melatonin

Comparative Analysis of Vertebrate Diurnal/Circadian Transcriptomes

Shift Work: Disrupted Circadian Rhythms and Sleep—Implications for Health and Well-being

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