Nuclear Receptors, Metabolism, and the Circadian Clock

Yang, Xiaoyong; Lamia, Katja; Evans, Ronald M.

doi:10.1101/sqb.2007.72.058

Cited by 82 publications

(74 citation statements)

References 70 publications

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“…At the cellular level, the clock influences, and is influenced by, circadian rhythms in metabolism; daily variations in glucose uptake and metabolism influence the clock through metabolic sensors, such as adenosine monophosphate-activated protein kinase (AMPK) [38]. Further, REV-ERBα is activated by haem, levels of which vary greatly in response to nutrient availability [39]. The synergy between clock function and cellular metabolism is beyond the scope of this review and has previously been described in detail (see [22,40]).…”

Section: The Internal Timing System and Metabolic Dysfunctionmentioning

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: The Internal Timing System and Metabolic Dysfunctionmentioning

confidence: 99%

Chronomedicine and type 2 diabetes: shining some light on melatonin

et al. 2016

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“…Circadian physiology reveals that strong connections between the circadian clock and cellular metabolism exist (1,(51)(52)(53)(54)(55)(56), but the extent to which these occur and the nature of these interactions have been largely unappreciated. This study reveals a comprehensive and integrative map of the diurnal metabolome in the liver and provides a detailed depiction of the dynamic interfaces between the metabolome, proteome, and transcriptome.…”

Section: Resultsmentioning

confidence: 99%

Coordination of the transcriptome and metabolome by the circadian clock

Eckel‐Mahan

Patel

Mohney

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

355

297

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The circadian clock governs a large array of physiological functions through the transcriptional control of a significant fraction of the genome. Disruption of the clock leads to metabolic disorders, including obesity and diabetes. As food is a potent zeitgeber (ZT) for peripheral clocks, metabolites are implicated as cellular transducers of circadian time for tissues such as the liver. From a comprehensive dataset of over 500 metabolites identified by mass spectrometry, we reveal the coordinate clock-controlled oscillation of many metabolites, including those within the amino acid and carbohydrate metabolic pathways as well as the lipid, nucleotide, and xenobiotic metabolic pathways. Using computational modeling, we present evidence of synergistic nodes between the circadian transcriptome and specific metabolic pathways. Validation of these nodes reveals that diverse metabolic pathways, including the uracil salvage pathway, oscillate in a circadian fashion and in a CLOCK-dependent manner. This integrated map illustrates the coherence within the circadian metabolome, transcriptome, and proteome and how these are connected through specific nodes that operate in concert to achieve metabolic homeostasis.C ircadian rhythms exist within a wide range of biological processes and control numerous aspects of physiology, including the sleep/wake cycle, eating, hormone and neurotransmitter secretion, and even cognitive function (1-4). Integral to the modern lifestyle is the ability to eat, sleep, work, exercise, and socialize around the clock and yet these allowances may serve as a preamble to obesity and other metabolic disorders. Recent studies reveal that a distorted circadian cycle can lead to aberrations in metabolism, producing symptoms such as obesity, insulin resistance, and others consistent with the metabolic syndrome (5-9). Whereas studies focused on night-shift and rotating shift workers emphasize the link between circadian rhythmicity and metabolism, rodent models of circadian arrhythmia also support this link (10-13). As an essential modulator of metabolism in vivo, the liver provides a cardinal domain in which to study interactions between the clock and metabolism as much of the liver transcriptome and proteome oscillates in expression or activity. These circadian characteristics of the liver are dependent largely on the zeitgeber (ZT), food (14-21).Precision within the circadian clock depends on nuclear transcriptional and translational feedback loops, but recent evidence that circadian, nontranscriptional, and nontranslational cytosolic rhythms crosstalk with nuclear rhythms to maintain circadian timing provides support for the idea that metabolites may affect the transcriptional-translational canonical clock system and vice versa (22,23). Some biochemical oscillations have been shown to cycle in a circadian fashion, such as calcium, 3′-5′-cyclic adenosine monophosphate (cAMP) and nicotinamide (NAD + ) (24-27). These oscillations feed into the clock system and can modulate circadian dynamics in vivo. Sever...

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“…As CRY and PER reach critical levels, they then bind directly to BMAL1/CLOCK and repress their own transcription (Darlington et al 1998;Shearman et al 2000;Reppert and Weaver 2001). Rev-erba directly represses transcription of Bmal1 and therefore serves as an additional feedback loop of circadian circuitry (Preitner et al 2002;Ueda et al 2002;Yin and Lazar 2005;Yang et al 2007). In addition to Bmal1, Rev-erba regulates metabolic genes, including glucose 6-phosphatase (Yin et al 2007), ApoCIII (Coste and Rodriguez 2002), and ElovI3 (Downes et al 1995), suggesting that this nuclear receptor (NR) links circadian rhythm to metabolism (Duez and Staels 2008).…”

mentioning

confidence: 99%

Negative feedback maintenance of heme homeostasis by its receptor, Rev-erbα

Wu¹,

Yin²,

Hanniman³

et al. 2009

Genes Dev.

107

101

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Intracellular heme levels must be tightly regulated to maintain proper mitochondrial respiration while minimizing toxicity, but the homeostatic mechanisms are not well understood. Here we report a novel negative feedback mechanism whereby the nuclear heme receptor Rev-erba tightly controls the level of its own ligand. Heme binding to Rev-erba recruits the NCoR/histone deacetylase 3 (HDAC3) corepressor complex to repress the transcription of the coactivator PGC-1a, a potent inducer of heme synthesis. Depletion of Rev-erba derepresses PGC-1a, resulting in increased heme levels. Conversely, increased Rev-erba reduces intracellular heme, and impairs mitochondrial respiration in a heme-dependent manner. Consistent with this bioenergetic impairment, overexpression of Rev-erba dramatically inhibits cell growth due to a cell cycle arrest. Thus, Rev-erba modulates the synthesis of its own ligand in a negative feedback pathway that maintains heme levels and regulates cellular energy metabolism.[Keywords: Rev-erba; PGC-1a; heme homeostasis; mitochondria; energy] Supplemental material is available at http://www.genesdev.org.

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Nuclear Receptors, Metabolism, and the Circadian Clock

Cited by 82 publications

References 70 publications

Chronomedicine and type 2 diabetes: shining some light on melatonin

Chronomedicine and type 2 diabetes: shining some light on melatonin

Coordination of the transcriptome and metabolome by the circadian clock

Negative feedback maintenance of heme homeostasis by its receptor, Rev-erbα

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