On time metabolism

Bass, Joseph

doi:10.1038/480466a

Cited by 8 publications

(4 citation statements)

References 15 publications

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“…Circadian rhythms are ~24-h cycles of physiologic processes, allowing organisms to synchronize with their environment (16, 51, 52). The circadian feedback loop is located in various tissues throughout the body known as peripheral clocks, which are entrained by the suprachiasmatic nucleus as well as various other factors including nutrients, hormones, and body temperature (1, 8, 14, 21, 44). Studies in mice have suggested that the liver, pancreas, skeletal muscle, kidneys, and small intestine all have peripheral circadian clocks (9, 17–20, 30, 39, 45, 55).…”

Section: Introductionmentioning

confidence: 99%

BMAL1 controls glucose uptake through paired-homeodomain transcription factor 4 in differentiated Caco-2 cells

Sussman

Stevenson

Mowdawalla

et al. 2019

American Journal of Physiology-Cell Physiology

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The transcription factor aryl hydrocarbon receptor nuclear translocator-like protein-1 (BMAL1) is an essential regulator of the circadian clock, which controls the 24-h cycle of physiological processes such as nutrient absorption. To examine the role of BMAL1 in small intestinal glucose absorption, we used differentiated human colon adenocarcinoma cells (Caco-2 cells). Here, we show that BMAL1 regulates glucose uptake in differentiated Caco-2 cells and that this process is dependent on the glucose transporter sodium-glucose cotransporter 1 (SGLT1). Mechanistic studies show that BMAL1 regulates glucose uptake by controlling the transcription of SGLT1 involving paired-homeodomain transcription factor 4 (PAX4), a transcriptional repressor. This is supported by the observation that clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated endonuclease Cas9 (Cas9) knockdown of PAX4 increases SGLT1 and glucose uptake. Chromatin immunoprecipitation (ChIP) and ChIP-quantitative PCR assays show that the knockdown or overexpression of BMAL1 decreases or increases the binding of PAX4 to the hepatocyte nuclear factor 1-α binding site of the SGLT1 promoter, respectively. These findings identify BMAL1 as a critical mediator of small intestine carbohydrate absorption and SGLT1.

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Section: Introductionmentioning

confidence: 99%

BMAL1 controls glucose uptake through paired-homeodomain transcription factor 4 in differentiated Caco-2 cells

Sussman

Stevenson

Mowdawalla

et al. 2019

American Journal of Physiology-Cell Physiology

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“…In addition to daily and monthly rhythms, the normal range for the human heartbeat is 60–100/min, [3] the respiratory rate is 12–20/min, gastric peristalsis occurs 3 times per min, [4,5] and neural oscillations have frequencies of 0.5–35 Hz [6] . Abnormal frequencies of circadian rhythms are associated with many mental and metabolic diseases, [7] including bipolar disorder, [8] anxiety, [9] depression, [10] schizophrenia, [11] sleep disorders, [12] diabetes, obesity and atherosclerosis [13,14] . Drugs to treat such dynamical diseases include domperidone, which stimulates gastric muscle contraction by antagonizing the inhibitory effect of dopamine on intermuscular neurons, increasing the amplitude and frequency of gastric antrum and duodenal peristalsis, thereby accelerating the rate of gastric solid‐liquid emptying [15] .…”

Section: Introductionmentioning

confidence: 99%

Peptide‐Modulated pH Rhythms

et al. 2022

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Many drugs adjust and/or control the spatiotemporal dynamics of periodic processes such as heartbeat, neuronal signaling and metabolism, often by interacting with proteins or oligopeptides.Here we use a quasi-biocompatible, non-equilibrium pH oscillatory system as a biomimetic biological clock to study the effect of pH-responsive peptides on rhythm dynamics. The added peptides generate feedback that can lengthen or shorten the oscillatory period during which the peptides alternate between random coil and coiled-coil conformations. This modulation of a chemical clock supports the notion that short peptide reagents may have utility as drugs to regulate human body clocks.

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“…What is striking about the majority of circadian mutant mouse lines is that in most cases they exhibit strong metabolic phenotypes (8), for example, the Rev-Erba/b and also Cry1/2 homozygous double knockout mice (16,132), and the Bmal1 -/ -knockout mouse (12) all exhibit profoundly disordered rhythms in behavior and dyslipidemia and impaired glucose homeostasis (8,76,86), with the latter being a model for the b-cell dysfunction, metabolic syndrome, and diabetes (86). This is frequently interpreted to mean that rhythmic cycling of the transcriptional ''core clock gene'' circuitry is essential for metabolic homeostasis.…”

Section: Cellular Clocksmentioning

confidence: 99%

Circadian Redox and Metabolic Oscillations in Mammalian Systems

O’Neill

Feeney

2014

Antioxidants & Redox Signaling

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Significance: A substantial proportion of mammalian physiology is organized around the day/night cycle, being regulated by the co-ordinated action of numerous cell-autonomous circadian oscillators throughout the body. Disruption of internal timekeeping, by genetic or environmental perturbation, leads to metabolic dysregulation, whereas changes in metabolism affect timekeeping. Recent Advances: While gene expression cycles are essential for the temporal coordination of normal physiology, it has become clear that rhythms in metabolism and redox balance are cell-intrinsic phenomena, which may regulate gene expression cycles reciprocally, but persist in their absence. For example, a circadian rhythm in peroxiredoxin oxidation was recently observed in isolated human erythrocytes, fibroblast cell lines in vitro, and mouse liver in vivo. Critical Issues: Mammalian timekeeping is a cellular phenomenon. While we understand many of the cellular systems that contribute to this biological oscillation's fidelity and robustness, a comprehensive mechanistic understanding remains elusive. Moreover, the formerly clear distinction between ''core clock components'' and rhythmic cellular outputs is blurred since several outputs, for example, redox balance, can feed back to regulate timekeeping. As with any cyclical system, establishing causality becomes problematic. Future Directions: A detailed molecular understanding of the temporal crosstalk between cellular systems, and the coincidence detection mechanisms that allow a cell to discriminate clock-relevant from irrelevant stimuli, will be essential as we move toward an integrated model of how this daily biological oscillation works. Such knowledge will highlight new avenues by which the functional consequences of circadian timekeeping can be explored in the context of human health and disease. Antioxid. Redox Signal. 20, 2966Signal. 20, -2981

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On time metabolism

Abstract: In mammals, molecular clocks regulate transcription and glucose homeostasis. One way they do so is by controlling glucocorticoid-receptor signalling, which suggests that clocks are embedded in liver metabolism.

Cited by 8 publications

References 15 publications

BMAL1 controls glucose uptake through paired-homeodomain transcription factor 4 in differentiated Caco-2 cells

BMAL1 controls glucose uptake through paired-homeodomain transcription factor 4 in differentiated Caco-2 cells

Peptide‐Modulated pH Rhythms

Circadian Redox and Metabolic Oscillations in Mammalian Systems

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