scholarly journals Night-time feeding of Bmal1−/− mice restores SCFA rhythms and their effect on ghrelin

2020 ◽  
Vol 245 (1) ◽  
pp. 155-164 ◽  
Author(s):  
Anneleen Segers ◽  
Louis Desmet ◽  
Shu Sun ◽  
Kristin Verbeke ◽  
Jan Tack ◽  
...  
Keyword(s):  
Clock Gene ◽  
Clock Genes ◽  
Short Chain Fatty Acids ◽  
Inhibitory Effect ◽  
Diurnal Rhythms ◽  
Feeding Time ◽  
Night Time ◽  
The Core ◽  
Core Clock Gene

The known crosstalk between short-chain fatty acids (SCFAs) and the circadian clock is tightly intertwined with feeding time. We aimed to investigate the role of the core clock gene Bmal1 and feeding time in the diurnal rhythms in plasma and caecal SCFA levels and in their effect on the release of the hunger hormone ghrelin in the stomach and colon. WT, Bmal1-/- (ad libitum fed) and night-time-restricted-fed (RF)-Bmal1-/- littermates were killed at zeitgeber time (ZT) 4 and 16. SCFA concentrations were measured by gas chromatography. To investigate the effect of SCFAs on ghrelin release, stomach and colonic full-thickness strips were incubated with Krebs or a SCFA mix mimicking plasma or caecal concentrations, after which octanoyl ghrelin release was measured by RIA. Diurnal rhythms in caecal and plasma SCFAs oscillated in phase but rhythmic changes were abolished in Bmal1-/- mice. RF of Bmal1-/- mice restored fluctuations in caecal SCFAs. Plasma SCFA concentrations failed to affect gastric ghrelin release. The effect of caecal SCFA concentrations on colonic ghrelin release was rhythmic (inhibition at ZT 4, no effect at ZT 16). In Bmal1-/- mice, the inhibitory effect of SCFAs at ZT 4 was abolished. RF Bmal1-/- mice restored the inhibitory effect and increased colonic Clock expression. To conclude, diurnal fluctuations in caecal SCFAs and the effect of SCFAs on colonic ghrelin release are regulated by feeding time, independent of the core clock gene Bmal1. However, local entrainment of other clock genes might contribute to the observed effects.

scholarly journals Circadian Expression of TIMP3 Is Disrupted by UVB Irradiation and Recovered by Green Tea Extracts

2019 ◽  
Vol 20 (4) ◽  
pp. 862 ◽  
Author(s):  
Sunyoung Park ◽  
Eun-Soo Lee ◽  
Nok-Hyun Park ◽  
Kyeonghwan Hwang ◽  
Eun-Gyung Cho
Keyword(s):  
Clock Gene ◽  
Regulatory Gene ◽  
Human Keratinocytes ◽  
Ultraviolet B ◽  
Rhythmic Expression ◽  
The Core ◽  
Circadian Expression ◽  
Tnf Α ◽  
Factor Α ◽  
Core Clock Gene

The human skin is the outermost physical barrier and has its own circadian machinery that works either cooperatively with the central clock, or autonomously. Circadian rhythms have been observed in many functions related to epidermal homeostasis including hydration and inflammation, and this functional oscillation is disturbed by ultraviolet radiation (UVR), which is a strong environmental cue. Among the genes estimated to show circadian expression in the skin, metalloproteinase inhibitor 3 (TIMP3), has a rhythmic expression in synchronized human keratinocytes similar to that of the core clock gene PER1 and an epidermal circadian regulatory gene, aquaporin 3 (AQP3) but was antiphase to the core clock gene BMAL1. Tumor necrosis factor-α (TNF-α), the regulatory target of TIMP3 via a disintegrin and metalloproteinase domain 17 (ADAM17), was inversely regulated when TIMP3 expression was downregulated by ultraviolet B (UVB) treatment. When synthetic TIMP3 peptides were applied to the cells, the secretion of TNF-α did not increase following the UVB treatment. Similar to TIMP3 peptides, Camellia sinensis leaf-derived extracts showed a distinguishing efficacy in recovering TIMP3 expression, downregulated by UVB treatment. Together, our results suggest that TIMP3 reversely mediates UVR-induced inflammation by being highly expressed during the daytime; therefore, recovering the circadian expression of TIMP3 using synthetic TIMP3 peptides or bioactive natural ingredients could at least in part inhibit the UVR-induced cellular phenomena.

scholarly journals Stromal Expression of the Core Clock Gene Period 2 Is Essential for Tumor Initiation and Metastatic Colonization

2020 ◽  
Vol 8 ◽  
Author(s):  
Lee Shaashua ◽  
Shimrit Mayer ◽  
Chen Lior ◽  
Hagar Lavon ◽  
Alexander Novoselsky ◽  
...  
Keyword(s):  
Clock Gene ◽  
Tumor Initiation ◽  
Metastatic Colonization ◽  
The Core ◽  
Period 2 ◽  
Core Clock Gene

scholarly journals Diurnal Amplitudes of Arterial Pressure and Heart Rate Are Dampened in Clock Mutant Mice and Adrenalectomized Mice

Endocrinology ◽  
2008 ◽  
Vol 149 (7) ◽  
pp. 3576-3580 ◽  
Author(s):  
Hiroyoshi Sei ◽  
Katsutaka Oishi ◽  
Sachiko Chikahisa ◽  
Kazuyoshi Kitaoka ◽  
Eiji Takeda ◽  
...  
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Clock Gene ◽  
Clock Genes ◽  
Plasma Aldosterone ◽  
Mutant Mice ◽  
Wild Type ◽  
Clock Mutant ◽  
Wild Type Control

Arterial pressure (AP), heart rate (HR), and cardiovascular diseases, including ischemic heart attack and cerebrovascular accident, show diurnal variation. Evidence that circadian-related genes contribute to cardiovascular control has been accumulated. In this study, we measured the AP and HR of Clock mutant mice on the Jcl/ICR background to determine the role of the Clock gene in cardiovascular function. Mice with mutated Clock genes had a dampened diurnal rhythm of AP and HR, compared with wild-type control mice, and this difference disappeared after adrenalectomy. The diurnal acrophase in both mean arterial pressure and HR was delayed significantly in Clock mutant mice, compared with wild-type mice, and this difference remained after adrenalectomy. Clock mutant mice had a lower concentration of plasma aldosterone, compared with wild-type mice. Our data suggest that the adrenal gland is involved in the diurnal amplitude, but not the acrophase, of AP and HR, and that the function of the Clock gene may be related to the nondipping type of AP elevation.

scholarly journals Deletion of the Clock Gene Period2 (Per2) in Glial Cells Alters Mood-Related Behavior in Mice

2020 ◽  
Author(s):  
Tomaz Martini ◽  
Jürgen A. Ripperger ◽  
Jimmy Stalin ◽  
Andrej Kores ◽  
Michael Stumpe ◽  
...  
Keyword(s):  
Glial Cells ◽  
Clock Gene ◽  
Clock Genes ◽  
Specific Expression ◽  
Adeno Associated Virus ◽  
Resistant Phenotype ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Physiological Pathways

AbstractThe circadian clock regulates many biochemical and physiological pathways, and lack of clock genes, such as Period (Per) 2, do not only affect circadian activity rhythms, but can also modulate food-anticipatory and mood-related behaviors. However, it is not known how cell-type specific expression of Per2 contributes to these behaviors. In this study, we find that Per2 in glial cells is important for balancing mood-related behaviors. Genetic and adeno-associated virus-mediated deletion of Per2 in glial cells of mice leads to a depression-resistant phenotype, as manifested in reduced despair and anxiety. This is paralleled by an increase of the GABA transporter 3 (Gat3) mRNA and a reduction of glutamate levels in the nucleus accumbens (NAc). Exclusive deletion of Per2 in glia of the NAc reduced despair, but had no influence on anxiety. Our data provide strong evidence for an important role of glial Per2 in regulating mood-related behavior.

scholarly journals The Adrenal Clock Prevents Aberrant Light-Induced Alterations in Circadian Glucocorticoid Rhythms

Endocrinology ◽  
2018 ◽  
Vol 159 (12) ◽  
pp. 3950-3964 ◽  
Author(s):  
William C Engeland ◽  
Logan Massman ◽  
Shubhendu Mishra ◽  
J Marina Yoder ◽  
Sining Leng ◽  
...  
Keyword(s):  
Molecular Clock ◽  
Clock Gene ◽  
Cholesterol Metabolism ◽  
Ex Vivo ◽  
Regulatory Protein ◽  
Steroidogenic Acute Regulatory Protein ◽  
Targeted Deletion ◽  
The Core ◽  
Steroidogenic Acute Regulatory ◽  
Core Clock Gene

Abstract The glucocorticoid (GC) rhythm is entrained to light-dark (LD) cycles via a molecular clock in the suprachiasmatic nucleus (SCN) and is maintained by an adrenal clock synchronized by SCN-dependent signals. Targeted deletion of the core clock gene Bmal1 can disrupt adrenal clock function. The requirement of the adrenal clock to stabilize the circadian GC rhythm during exposure to aberrant LD cycles was determined using novel aldosterone synthase (AS)Cre/+::Bmal1Fl/Fl mice in which Bmal1 deletion occurred during postnatal adrenal transdifferentiation. To examine whether adrenal Bmal1 deletion results in loss of the adrenal clock, mice were crossed with mPER2::Luciferase (mPER2Luc/+) mice. Adrenals from ASCre/+::Bmal1+/+::PER2Luc/+ [control (CTRL)] mice show mPER2Luc rhythms ex vivo, whereas slices from ASCre/+::Bmal1Fl/Fl::PER2Luc/+ [knockout (KO)] mice show dampened rhythms. To monitor corticosterone rhythmicity, mice were implanted with subcutaneous microdialysis probes and sampled at 60-minute intervals for up to 3 days under 12:12-hour [τ (T) 24] LD or 3.5:3.5-hour (T7) LD cycles. Corticosterone rhythms were entrained to T24 LD in CTRL and KO mice. Under T7 LD, circadian corticosterone rhythms persisted in most CTRL mice but not KO mice. Hyperadrenocorticism also was observed in KO mice under T7 LD, reflected by increased corticosterone peak amplitude, total daily corticosterone, and responses to ACTH. Analysis of dysregulated adrenal genes in KO mice exposed to aberrant light identified candidates involved in cholesterol metabolism and trafficking, including steroidogenic acute regulatory protein, which could increase steroidogenesis. Our results show that the adrenal clock functions to buffer steroidogenic responses to aberrant light and stabilize circadian GC rhythmicity.

scholarly journals Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma

2017 ◽  
Vol 32 (2) ◽  
pp. 121-129 ◽  
Author(s):  
Emily A. Slat ◽  
Jasmin Sponagel ◽  
Luciano Marpegan ◽  
Tatiana Simon ◽  
Najla Kfoury ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Growth Inhibition ◽  
Clock Gene ◽  
Daily Rhythms ◽  
The Core ◽  
Circadian Time ◽  
Damage Response ◽  
Human And Mouse ◽  
Core Clock Gene

The safety and efficacy of chemotherapeutics can vary as a function of the time of their delivery during the day. This study aimed to improve the treatment of glioblastoma (GBM), the most common brain cancer, by testing whether the efficacy of the DNA alkylator temozolomide (TMZ) varies with the time of its administration. We found cell-intrinsic, daily rhythms in both human and mouse GBM cells. Circadian time of treatment affected TMZ sensitivity of murine GBM tumor cells in vitro. The maximum TMZ-induced DNA damage response, activation of apoptosis, and growth inhibition occurred near the daily peak in expression of the core clock gene Bmal1. Deletion of Bmal1 (Arntl) abolished circadian rhythms in gene expression and TMZ-induced activation of apoptosis and growth inhibition. These data indicate that tumor cell-intrinsic circadian rhythms are common to GBM tumors and can regulate TMZ cytotoxicity. Optimization of GBM treatment by timing TMZ administration to daily rhythms should be evaluated in prospective clinical trials.

scholarly journals The Controversial Role of Human Gut Lachnospiraceae

2020 ◽  
Vol 8 (4) ◽  
pp. 573 ◽  
Author(s):  
Mirco Vacca ◽  
Giuseppe Celano ◽  
Francesco Maria Calabrese ◽  
Piero Portincasa ◽  
Marco Gobbetti ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Intestinal Lumen ◽  
Human Gut ◽  
The Core ◽  
Host Diet ◽  
Health And Disease ◽  
Host Physiology

The complex polymicrobial composition of human gut microbiota plays a key role in health and disease. Lachnospiraceae belong to the core of gut microbiota, colonizing the intestinal lumen from birth and increasing, in terms of species richness and their relative abundances during the host’s life. Although, members of Lachnospiraceae are among the main producers of short-chain fatty acids, different taxa of Lachnospiraceae are also associated with different intra- and extraintestinal diseases. Their impact on the host physiology is often inconsistent across different studies. Here, we discuss changes in Lachnospiraceae abundances according to health and disease. With the aim of harnessing Lachnospiraceae to promote human health, we also analyze how nutrients from the host diet can influence their growth and how their metabolites can, in turn, influence host physiology.

scholarly journals Timing of expression of the core clock gene Bmal1 influences its effects on aging and survival

2016 ◽  
Vol 8 (324) ◽  
pp. 324ra16-324ra16 ◽  
Author(s):  
Guangrui Yang ◽  
Lihong Chen ◽  
Gregory R. Grant ◽  
Georgios Paschos ◽  
Wen-Liang Song ◽  
...  
Keyword(s):  
Clock Gene ◽  
The Core ◽  
Core Clock Gene

scholarly journals Rhythmic clock gene expression in Atlantic salmon parr brain

2021 ◽  
Author(s):  
Charlotte Bolton ◽  
Michael Bekaert ◽  
Mariann Eilertsen ◽  
Jon Vidar Helvik ◽  
Herve Migaud
Keyword(s):  
Atlantic Salmon ◽  
Clock Gene ◽  
Clock Genes ◽  
Clock Gene Expression ◽  
Sister Clade ◽  
Before And After ◽  
Salmon Parr ◽  
Species Specific ◽  
Atlantic Salmon Parr

To better understand the complexity of clock genes in salmonids, a taxon with an additional whole genome duplication, an analysis was performed to identify and classify gene family members (clock, arntl, period, cryptochrome, nr1d, ror, and csnk1). The majority of clock genes in zebrafish and Northern pike, appeared to be duplicated. In comparison to the 29 clock genes described in zebrafish, 48 clock genes were discovered in salmonid species. There was also evidence of species-specific reciprocal gene losses conserved to the Oncorhynchus sister clade. From the six period genes identified four were highly significantly rhythmically expressed (per1a.1, per1a.2, per1b, per2b) and one was marginally significantly rhythmically expressed (per2a). The transcriptomic study of juvenile Atlantic salmon (parr) brain tissues confirmed gene identification and revealed that there were 1,642 rhythmically expressed genes (p < 0.001), of which 12 were clock genes. The majority of rhythmically expressed genes peaked two hours before and after daylight. These findings provide a foundation for further research into the function of clock genes circadian rhythmicity and the role of an enriched number of clock genes relating to seasonal driven life history in salmonids.

scholarly journals REVIEW OF RESEARCH ON THE RELATIONSHIP BETWEEN CIRCADIAN RHYTHMS AND CARCINOGENESIS USING ANIMAL MODELS

2021 ◽  
Vol 20 (3) ◽  
pp. 134-143
Author(s):  
G. S. Kireeva ◽  
E. A. Gubareva ◽  
M. A. Maydin ◽  
A. V. Panchenko ◽  
M. L. Tyndyk ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Animal Models ◽  
Clock Gene ◽  
Clock Genes ◽  
Tumor Development ◽  
Malignant Neoplasms ◽  
Light Cycle ◽  
Gene System ◽  
The Relationship

Purpose of the study: to review in vivo studies on the relationship and role of various molecular genetic components of the circadian rhythm system in the initiation and development of malignant neoplasms. in contrast to clinical and epidemiological studies, animal models, including transgenic animal models, can model various changes and disturbances in the activity of clock genes and track the results of these changes.Material and Methods. the review includes data from studies carried out over the past 10 years in animal models, studying the mechanisms and effects of disturbances in the system of circadian rhythms related to the formation and development of tumors. the data sources for the review were the Medline, embase and scopus databases.Results. analysis of the literature has shown that interference with the work of the «biological clock» by changing the light cycle, disrupting the expression of clock genes and other manipulations is a factor predisposing to the development of tumors. in tumors of various types, the expression of clock genes is often mismatched, and it is unclear at what stage of their formation this occurs. in addition, the development of tumors disrupts the circadian homeostasis of the body. there are three key areas of research aimed at studying the role of circadian rhythms in tumor development: disturbance of circadian rhythms as a carcinogenic factor, disturbances in the clock gene system in a tumor, disturbances in the clock gene system of the whole organism, provoked by tumor development.Conclusion. the results of studies on animal models demonstrate that the relationship between the disturbance of circadian rhythms and the tumor process is complex since the causal relationship has not yet been studied. in this regard, the prospect of targeted pharmacological correction of circadian rhythms in clinical practice in cancer patients does not seem to be the nearest one.

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