Circadian rhythms in liver metabolism and disease

Ferrell, Jessica M.; Chiang, John Y.L.

doi:10.1016/j.apsb.2015.01.003

Cited by 98 publications

(89 citation statements)

References 118 publications

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“…Many studies have demonstrated the effects of normal circadian action on health and the disruption of circadian rhythm, which can have adverse effects on metabolic function (2,3). Several people work at night or work a rotating shift, employed as police, doctors and nurses and airport services.…”

Section: Aimsmentioning

confidence: 99%

Study of association between beverage consumption pattern and lipid profile in shift workers

Mashhadi

Saadat

Afsharmanesh

et al. 2016

Diabetes & Metabolic Syndrome: Clinical Research & Revi

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Section: Aimsmentioning

confidence: 99%

Study of association between beverage consumption pattern and lipid profile in shift workers

Mashhadi

Saadat

Afsharmanesh

et al. 2016

Diabetes & Metabolic Syndrome: Clinical Research & Revi

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“…Shift work-induced circadian misalignment is associated with higher rates of metabolic, cardiovascular, and neoplastic disease. Clinical experience suggests time of day can have a marked effect on disease severity (2)(3)(4). Indeed, the majority of the best-selling prescription drugs and World Health Organization essential medicines target molecules that oscillate in mice (1).…”

mentioning

confidence: 99%

CYCLOPS reveals human transcriptional rhythms in health and disease

Anafi

Francey

Hogenesch

et al. 2017

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

208

247

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Circadian rhythms modulate many aspects of physiology. Knowledge of the molecular basis of these rhythms has exploded in the last 20 years. However, most of these data are from model organisms, and translation to clinical practice has been limited. Here, we present an approach to identify molecular rhythms in humans from thousands of unordered expression measurements. Our algorithm, cyclic ordering by periodic structure (CYCLOPS), uses evolutionary conservation and machine learning to identify elliptical structure in high-dimensional data. From this structure, CYCLOPS estimates the phase of each sample. We validated CYCLOPS using temporally ordered mouse and human data and demonstrated its consistency on human data from two independent research sites. We used this approach to identify rhythmic transcripts in human liver and lung, including hundreds of drug targets and disease genes. Importantly, for many genes, the circadian variation in expression exceeded variation from genetic and other environmental factors. We also analyzed hepatocellular carcinoma samples and show these solid tumors maintain circadian function but with aberrant output. Finally, to show how this method can catalyze medical translation, we show that dosage time can temporally segregate efficacy from dose-limiting toxicity of streptozocin, a chemotherapeutic drug. In sum, these data show the power of CYCLOPS and temporal reconstruction in bridging basic circadian research and clinical medicine.gene expression | biological rhythms | machine learning | autoencoder | circadian rhythms C ircadian rhythms are nearly ubiquitous in nature. In animals, much of physiology and behavior is under circadian control. Body temperature, hormonal rhythms, blood pressure, and locomotor activity are just a few of the processes displaying daily rhythms. In circadian model systems (e.g., cyanobacteria, Neurospora, Arabidopsis, Drosophila, and mice), high-resolution time sampling is straightforward, and experiments show that a substantial fraction of the transcriptome is under clock control. For example, in mice, a majority of genes are clock regulated in at least 1 of 12 different organs (1).Circadian rhythms are also critical for humans. Shift work-induced circadian misalignment is associated with higher rates of metabolic, cardiovascular, and neoplastic disease. Clinical experience suggests time of day can have a marked effect on disease severity (2-4). Indeed, the majority of the best-selling prescription drugs and World Health Organization essential medicines target molecules that oscillate in mice (1). However, translation of these findings to clinical medicine remains slow. How does human molecular physiology change with circadian time? In mice, and presumably humans, circadian output genes are markedly different in each tissue. Obviously, repeated sampling from most human organs is not possible. As a result, we have limited ability to study human molecular rhythms and relate them to either normal or disease physiology.One approach is to analyze temporally ...

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“…Clock and Bmal1 form a heterodimer and transactivate through E-Box elements the Per (Period-1 and 2) and Cry genes (Cryptochrome-1 and 2). Per and Cry proteins in turn interact with Clock/Bmal1 and attenuate their own transactivation [5, 8, 17]. In addition to Clock/Bmal1, we and other investigators have demonstrated that DEC transcription factors, differentiated embryo chondrocyte-1 and 2, are strong E-box binding proteins [18–20].…”

Section: Introductionmentioning

confidence: 97%

Circadian rhythmicity: A functional connection between differentiated embryonic chondrocyte-1 (DEC1) and small heterodimer partner (SHP)

Marczak

Yan

2017

Archives of Biochemistry and Biophysics

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Circadian rhythm misalignment has been increasingly recognized to pose health risk for a wide range of diseases, particularly metabolic disorders. The liver maintains metabolic homeostasis and expresses many circadian genes, such as differentiated embryo chondrocyte-1 (DEC1) and small heterodimer partner (SHP). DEC1 is established to repress transcription through E-box elements, and SHP belongs to the superfamily of nuclear receptors and has multiple E-box elements in its promoter. Importantly, DEC1 and SHP are inversely oscillated. This study was performed to test the hypothesis that the SHP gene is a target gene of DEC1. Cotransfection demonstrated that DEC1 repressed the SHP promoter and attenuated the transactivation of the classic circadian activator complex of Clock/Bmal1. Site-directed mutagenesis, electrophoretic mobility shift assay and chromatin immunoprecipitation established that the repression was achieved through the E-box in the proximal promoter. Transfection of DEC1 suppressed the expression of SHP. In circadian-inducing cells, the epileptic agent valproate inversely altered the expression of DEC1 and SHP. Both DEC1 and SHP are involved in energy balance and valproate is known to induce hepatic steatosis. Our findings collectively establish that DEC1 participates in the negative loop of SHP oscillating expression with potential implications in metabolic homeostasis.

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Circadian rhythms in liver metabolism and disease

Cited by 98 publications

References 118 publications

Study of association between beverage consumption pattern and lipid profile in shift workers

Study of association between beverage consumption pattern and lipid profile in shift workers

CYCLOPS reveals human transcriptional rhythms in health and disease

Circadian rhythmicity: A functional connection between differentiated embryonic chondrocyte-1 (DEC1) and small heterodimer partner (SHP)

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