scholarly journals Rhythmic Food Intake Drives Rhythmic Gene Expression More Potently than the Hepatic Circadian Clock in Mice

Cell Reports ◽  
2019 ◽  
Vol 27 (3) ◽  
pp. 649-657.e5 ◽  
Author(s):  
Ben J. Greenwell ◽  
Alexandra J. Trott ◽  
Joshua R. Beytebiere ◽  
Shanny Pao ◽  
Alexander Bosley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Circadian Clock ◽  
Rhythmic Gene

Rhythmic Food Intake Drives Rhythmic Gene Expression More Potently than the Hepatic Circadian Clock in Mice

2019 ◽  
Author(s):  
Ben Greenwell ◽  
Alexandra Trott ◽  
Joshua Beytebiere ◽  
Shanny Pao ◽  
Alexander Bosley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Circadian Clock ◽  
Rhythmic Gene

scholarly journals The hepatocyte insulin receptor is required to program rhythmic gene expression and the liver clock

2021 ◽  
Author(s):  
Tiffany Fougeray ◽  
Arnaud Polizzi ◽  
Marion Régnier ◽  
Anne Fougerat ◽  
Sandrine Ellero-Simatos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Circadian Clock ◽  
Insulin Receptor ◽  
Mammalian Cells ◽  
Metabolic Diseases ◽  
Hepatic Glucose Production ◽  
Hepatic Insulin Resistance ◽  
Alcoholic Fatty Liver ◽  
Rhythmic Gene

SUMMARYIn mammalian cells, gene expression is rhythmic and sensitive to various environmental and physiological stimuli. A circadian clock system helps to anticipate and synchronize gene expression with daily stimuli including cyclic light and food intake, which control the central and peripheral clock programs, respectively. Food intake also regulates insulin secretion. How much insulin contributes to the effect of feeding on the entrainment of the clock and rhythmic gene expression remains to be investigated.An important component of insulin action is mediated by changes in insulin receptor (IR)-dependent gene expression. In the liver, insulin at high levels controls the transcription of hundreds of genes involved in glucose homeostasis to promote energy storage while repressing the expression of gluconeogenic genes. In type 2 diabetes mellitus (T2DM), selective hepatic insulin resistance impairs the inhibition of hepatic glucose production while promoting lipid synthesis. This pathogenic process promoting hyperlipidemia as well as non-alcoholic fatty liver diseases.While several lines of evidence link such metabolic diseases to defective control of circadian homeostasis, the hypothesis that IR directly synchronizes the clock has not been studied in vivo. Here, we used conditional hepatocyte-restricted gene deletion to evaluate the role of IR in the regulation and oscillation of gene expression as well as in the programming of the circadian clock in adult mouse liver.

scholarly journals Critical role of deadenylation in regulating poly(A) rhythms and circadian gene expression

2019 ◽  
Author(s):  
Xiangyu Yao ◽  
Shihoko Kojima ◽  
Jing Chen
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Transcriptional Control ◽  
Critical Role ◽  
Tail Length ◽  
Circadian Gene ◽  
Gene Expression Control ◽  
Rhythmic Gene ◽  
Transcriptional Controls

AbstractThe mammalian circadian clock is deeply rooted in rhythmic regulation of gene expression. Rhythmic transcriptional control mediated by the circadian transcription factors is thought to be the main driver of mammalian circadian gene expression. However, mounting evidence has demonstrated the importance of rhythmic post-transcriptional controls, and it remains unclear how the transcriptional and post-transcriptional mechanisms collectively control rhythmic gene expression. A recent study discovered rhythmicity in poly(A) tail length in mouse liver and its strong correlation with protein expression rhythms. To understand the role of rhythmic poly(A) regulation in circadian gene expression, we constructed a parsimonious model that depicts rhythmic control imposed upon basic mRNA expression and poly(A) regulation processes, including transcription, deadenylation, polyadenylation, and degradation. The model results reveal the rhythmicity in deadenylation as the strongest contributor to the rhythmicity in poly(A) tail length and the rhythmicity in the abundance of the mRNA subpopulation with long poly(A) tails (a rough proxy for mRNA translatability). In line with this finding, the model further shows that the experimentally observed distinct peak phases in the expression of deadenylases, regardless of other rhythmic controls, can robustly group the rhythmic mRNAs by their peak phases in poly(A) tail length and in abundance of the subpopulation with long poly(A) tails. This provides a potential mechanism to synchronize the phases of target gene expression regulated by the same deadenylases. Our findings highlight the critical role of rhythmic deadenylation in regulating poly(A) rhythms and circadian gene expression.Author SummaryThe biological circadian clock regulates various bodily functions such that they anticipate and respond to the day-and-night cycle. To achieve this, the circadian clock controls rhythmic gene expression, and these genes ultimately drive the rhythmicity of downstream biological processes. As a mechanism of driving circadian gene expression, rhythmic transcriptional control has attracted the central focus. However, mounting evidence has also demonstrated the importance of rhythmic post-transcriptional controls. Here we use mathematical modeling to investigate how transcriptional and post-transcriptional rhythms coordinately control rhythmic gene expression. We have particularly focused on rhythmic regulation of the length of poly(A) tail, a nearly universal feature of mRNAs that controls mRNA stability and translation. Our model reveals that the rhythmicity of deadenylation, the process that shortens the poly(A) tail, is the dominant contributor to the rhythmicity in poly(A) tail length and mRNA translatability. Particularly, the phase of deadenylation nearly overrides the other rhythmic processes in controlling the phases of poly(A) tail length and mRNA translatability. Our finding highlights the critical role of rhythmic deadenylation in circadian gene expression control.

scholarly journals Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

2015 ◽  
Vol 112 (47) ◽  
pp. E6579-E6588 ◽  
Author(s):  
Florian Atger ◽  
Cédric Gobet ◽  
Julien Marquis ◽  
Eva Martin ◽  
Jingkui Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Mouse Liver ◽  
Mitochondrial Activity ◽  
Translation Efficiency ◽  
Mrna Transcription ◽  
Mrna Accumulation ◽  
Feeding Rhythms ◽  
Rhythmic Gene ◽  
Living Organisms

Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light–dark conditions and ad libitum or night-restricted feeding in WT and brain and muscle Arnt-like 1 (Bmal1)-deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5′-Terminal Oligo Pyrimidine tract (5′-TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5′-UTR (TISU) motif. The increased translation efficiency of 5′-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation.

scholarly journals Systematic analysis of differential rhythmic liver gene expression mediated by the circadian clock and feeding rhythms

2021 ◽  
Vol 118 (3) ◽  
pp. e2015803118
Author(s):  
Benjamin D. Weger ◽  
Cédric Gobet ◽  
Fabrice P. A. David ◽  
Florian Atger ◽  
Eva Martin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Mrna Expression ◽  
Restricted Feeding ◽  
Wild Type ◽  
Expression Levels ◽  
Genetic Ablation ◽  
Feeding Rhythms ◽  
Rhythmic Gene ◽  
Ad Libitum

The circadian clock and feeding rhythms are both important regulators of rhythmic gene expression in the liver. To further dissect the respective contributions of feeding and the clock, we analyzed differential rhythmicity of liver tissue samples across several conditions. We developed a statistical method tailored to compare rhythmic liver messenger RNA (mRNA) expression in mouse knockout models of multiple clock genes, as well as PARbZip output transcription factors (Hlf/Dbp/Tef). Mice were exposed to ad libitum or night-restricted feeding under regular light–dark cycles. During ad libitum feeding, genetic ablation of the core clock attenuated rhythmic-feeding patterns, which could be restored by the night-restricted feeding regimen. High-amplitude mRNA expression rhythms in wild-type livers were driven by the circadian clock, but rhythmic feeding also contributed to rhythmic gene expression, albeit with significantly lower amplitudes. We observed that Bmal1 and Cry1/2 knockouts differed in their residual rhythmic gene expression. Differences in mean expression levels between wild types and knockouts correlated with rhythmic gene expression in wild type. Surprisingly, in PARbZip knockout mice, the mean expression levels of PARbZip targets were more strongly impacted than their rhythms, potentially due to the rhythmic activity of the D-box–repressor NFIL3. Genes that lost rhythmicity in PARbZip knockouts were identified to be indirect targets. Our findings provide insights into the diurnal transcriptome in mouse liver as we identified the differential contributions of several core clock regulators. In addition, we gained more insights on the specific effects of the feeding–fasting cycle.

Anti-Diabetic and Angio-Protective Effect of Guluronic Acid (G2013) as a New Nonsteroidal Anti-Inflammatory Drug in the Experimental Model of Diabetes

2020 ◽  
Vol 20 (3) ◽  
pp. 446-452
Author(s):  
Seyed S. Mortazavi-Jahromi ◽  
Shahab Alizadeh ◽  
Mohammad H. Javanbakht ◽  
Abbas Mirshafiey
Keyword(s):  
Gene Expression ◽  
Blood Glucose ◽  
Food Intake ◽  
Experimental Model ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Diabetic Control ◽  
The Body ◽  
Sprague Dawley ◽  
Guluronic Acid

Background: This study aimed to investigate the effects of guluronic acid (G2013) on blood sugar, insulin, and gene expression profile of oxLDL receptors (SR-A, CD36, LOX-1, and CD68) in the experimental model of diabetes. Methods: 18 Sprague Dawley rats were randomly assigned to three groups of healthy control, diabetic control, and G2013 group. Diabetes was induced through intraperitoneal (IP) injection of 60 mg/kg streptozotocin. The subjects were IP treated with 25 mg/kg of G2013 per day for 28 days. The body weight, food intake, fasting blood glucose and insulin were measured. In addition, the expression of mentioned genes was investigated through quantitative real-time PCR. Results: The data showed that the final weight increased significantly in the G2013-treated subjects compared to the diabetic control (p < 0.05). The results indicated that final food intake significantly reduced in the G2013-treated subjects compared to the diabetic control (p < 0.05). The study findings also suggested that the final fasting blood glucose significantly reduced in the G2013-treated group, whereas the final fasting serum insulin level significantly increased in this group compared to the diabetic control (p < 0.05). Moreover, the gene expression levels of SR-A, CD36, LOX-1, and CD68 in the G2013 group significantly reduced compared to the diabetic control (p < 0.05). Conclusion: This study showed that G2013, could reduce blood glucose and increase insulin levels and reduce the gene expression level of oxLDL receptors. In addition, it may probably play an important role in reducing the severity of diabetes-induced inflammatory symptoms.

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