Molecular mechanisms and physiological importance of circadian rhythms

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 21(2), P. 67 - 84

Published: Nov. 25, 2019

Language: Английский

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Circadian physiology of metabolism

Science, Journal Year: 2016, Volume and Issue: 354(6315), P. 1008 - 1015

Published: Nov. 24, 2016

A majority of mammalian genes exhibit daily fluctuations in expression levels, making circadian rhythms the largest known regulatory network normal physiology. Cell-autonomous clocks interact with light-dark and feeding-fasting cycles to generate approximately 24-hour oscillations function thousands genes. Circadian secreted molecules signaling components transmits timing information between cells tissues. Such intra- intercellular optimize physiology both by managing energy use temporally segregating incompatible processes. Experimental animal models epidemiological data indicate that chronic rhythm disruption increases risk metabolic diseases. Conversely, time-restricted feeding, which imposes feeding fasting without caloric reduction, sustains robust diurnal can alleviate These findings highlight an integrative role offer a new perspective for treating diseases is hallmark.

Language: Английский

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Circadian clocks and insulin resistance

Nature Reviews Endocrinology, Journal Year: 2018, Volume and Issue: 15(2), P. 75 - 89

Published: Dec. 7, 2018

Language: Английский

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Molecular and Cellular Mechanisms of Cardiovascular Disorders in Diabetes

Circulation Research, Journal Year: 2016, Volume and Issue: 118(11), P. 1808 - 1829

Published: May 26, 2016

The clinical correlations linking diabetes mellitus with accelerated atherosclerosis, cardiomyopathy, and increased post-myocardial infarction fatality rates are increasingly understood in mechanistic terms. multiple mechanisms discussed this review seem to share a common element: prolonged increases reactive oxygen species (ROS) production diabetic cardiovascular cells. Intracellular hyperglycemia causes excessive ROS production. This activates nuclear poly(ADP-ribose) polymerase, which inhibits GAPDH, shunting early glycolytic intermediates into pathogenic signaling pathways. polymerase also reduce sirtuin, PGC-1α, AMP-activated protein kinase activity. These changes cause decreased mitochondrial biogenesis, production, disturbed circadian clock synchronization of glucose lipid metabolism. Excessive facilitates transport proatherogenic transcription factors, the neutrophil enzyme initiating NETosis, peptidylarginine deiminase 4, NOD-like receptor family, pyrin domain-containing 3 inflammasome. Insulin resistance cardiomyocyte by increasing fatty acid flux oxidation. stimulates overexpression PPARα translocation forkhead box O 1, cardiomyopathy. shift balance between fusion fission favor fission, reducing metabolic capacity efficiency electron chain ATP synthesis. Mitochondrial oxidative stress plays central role angiotensin II–induced gap junction remodeling arrhythmogenesis. contribute sudden death diabetics after myocardial post-translational modifications, ryanodine phosphorylation downregulation sarco-endoplasmic reticulum Ca ++ -ATPase transcription. Increased depress autonomic ganglion synaptic transmission oxidizing nAch α3 subunit, potentially contributing risk fatal cardiac arrhythmias associated neuropathy.

Language: Английский

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Genomics of circadian rhythms in health and disease

Genome Medicine, Journal Year: 2019, Volume and Issue: 11(1)

Published: Dec. 1, 2019

Abstract Circadian clocks are endogenous oscillators that control 24-h physiological and behavioral processes. The central circadian clock exerts over myriad aspects of mammalian physiology, including the regulation sleep, metabolism, immune system. Here, we review advances in understanding genetic sleep through system, as well impact dysregulated gene expression on metabolic function. We also recent studies have begun to unravel clock’s role controlling cardiovascular nervous systems, gut microbiota, cancer, aging. Such these systems relies, part, transcriptional regulation, with evidence for genome-wide chromosome organization. These novel insights into genomic human physiology provide opportunities discovery improved treatment strategies new biological underpinnings disease.

Language: Английский

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Role of the circadian system in cardiovascular disease

Journal of Clinical Investigation, Journal Year: 2018, Volume and Issue: 128(6), P. 2157 - 2167

Published: May 31, 2018

All species organize behaviors to optimally match daily changes in the environment, leading pronounced activity/rest cycles that track light/dark cycle. Endogenous, approximately 24-hour circadian rhythms brain, autonomic nervous system, heart, and vasculature prepare cardiovascular system for optimal function during these anticipated behavioral cycles. Cardiovascular rhythms, however, may be a double-edged sword. The normal amplified responses morning aid transition from sleep activity, but such exaggerated are potentially perilous individuals susceptible adverse events. Indeed, occurrence of stroke, myocardial infarction, sudden cardiac death all have patterns, striking most frequently morning. Furthermore, chronic disruptions clock, as with night-shift work, contribute increased risk. Here we highlight importance disease, identify opportunities optimizing timing medications disease.

Language: Английский

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Interplay between Circadian Clock and Cancer: New Frontiers for Cancer Treatment

Trends in cancer, Journal Year: 2019, Volume and Issue: 5(8), P. 475 - 494

Published: Aug. 1, 2019

Language: Английский

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Medicine in the Fourth Dimension

Cell Metabolism, Journal Year: 2019, Volume and Issue: 30(2), P. 238 - 250

Published: Aug. 1, 2019

Language: Английский

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Citrus polymethoxyflavones attenuate metabolic syndrome by regulating gut microbiome and amino acid metabolism

Science Advances, Journal Year: 2020, Volume and Issue: 6(1)

Published: Jan. 3, 2020

Metabolic syndrome (MetS) is intricately linked to dysregulation of gut microbiota and host metabolomes. Here, we first find that a purified citrus polymethoxyflavone-rich extract (PMFE) potently ameliorates high-fat diet (HFD)-induced MetS, alleviates dysbiosis, regulates branched-chain amino acid (BCAA) metabolism using 16S rDNA amplicon sequencing metabolomic profiling. The metabolic protective effects PMFE are dependent, as demonstrated by antibiotic treatment fecal microbiome transplantation (FMT). modulation altered BCAA levels in the serum feces, which were significantly associated with features actively responsive therapeutic interventions PMFE. Notably, greatly enriched commensal bacterium Bacteroides ovatus, gavage B. ovatus reduced concentrations alleviated MetS HFD mice. may be used prebiotic agent attenuate target-specific microbial species have unique promise for diseases.

Language: Английский

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Circadian rhythm as a therapeutic target

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(4), P. 287 - 307

Published: Feb. 15, 2021

Language: Английский

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