Transcriptomic changes in Drosophila tissues under Time-restricted Feeding (TRF)
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ABSTRACT: Next generation sequencing was used to assess the changes along a diurnal cycle in the transcriptome of Drosophila head, periphery (entire body except the head) or the heart at 3, 5 or 7 weeks of age under ad libitum feeding (ALF) or time-restricted feeding (TRF). Next generation sequencing was used to assess the changes along a diurnal cycle in the transcriptome of Drosophila head, periphery (entire body except the head) or the heart at 3, 5 or 7 weeks of age under ad libitum feeding (ALF) or time-restricted feeding (TRF).
Project description:Next generation sequencing was used to assess the changes along a diurnal cycle in the transcriptome of Drosophila head, periphery (entire body except the head) or the heart at 3, 5 or 7 weeks of age under ad libitum feeding (ALF) or time-restricted feeding (TRF).
Project description:The goal of the study was to investigate the mechanistic basis for Time-restricted feeding (TRF) improvement in skeletal muscle by assessing transcriptomic data of wild type (WT), WT under High-fat diet (HFD), and genetic obesity linked mutant sphingosine kinase 2 (Sk2) under ad libitum feeding (ALF) and time-restricted feeding (TRF) conditions. Next generation sequencing was used to assess the changes along a diurnal cycle in the transcriptome of Drosophila indirect flight muscle (IFM) tissue at 3-week of age under ad libitum feeding (ALF) or time-restricted feeding (TRF).
Project description:Time-restricted feeding (TRF) is an emerging behavioral nutrition intervention that sustains a daily cycle of feeding and fasting. TRF in animals and humans has shown pleiotropic health benefits arising from multiple organ systems, yet the molecular basis of TRF is not well understood. We subjected mice to isocaloric ad libitum feeding (ALF) or TRF of Western diet, and examined gene expression changes in 22 different brain regions and peripheral organs collected every 2 hour over 24 hour. We discovered TRF profoundly impacts gene expression. Nearly 80% of genes show significant differential expression or rhythmicity under TRF in at least one tissue. Functional annotation of these changes highlight tissue and pathway specific impacts of TRF. These findings and resources will offer a framework for future mechanistic studies, and guide human TRE interventions for various disease conditions with or without pharmacotherapies.
Project description:Meal timing is essential in synchronization of circadian rhythms in different organ systems through clock-dependent and -independent mechanisms. Adipose tissue is a critical metabolic and endocrine organ whose circadian clock and transcriptome can be reset by meal timing. However, it remains largely unexplored how circadian rhythms in adipose tissue are organized in time-restricted feeding that intervenes meal timing. Here, we applied quantitative phospho-proteomics to characterize circadian features associated with ad libitum feeding (ALF), day/inactive phase-restricted feeding (DRF) and night/active phase-restricted feeding (NRF) in female mice.
Project description:Using high throughput sequencing of Drosophila head RNA, a small set of miRNAs that undergo robust circadian oscillations in levels were discovered. We concentrated on a cluster of six miRNAs, mir-959-964, all of which peak at about ZT12 or lights-off. The data indicate that the cluster pri-miRNA is transcribed under bona fide circadian transcriptional control and that all 6 mature miRNAs have short half-lives, a requirement for oscillating. Manipulation of food intake dramatically affects the levels and timing of cluster miRNA transcription with no more than minor effects on the core circadian oscillator. This indicates that the central clock regulates feeding, which in turn regulates proper levels and cycling of the cluster miRNAs. Viable Gal4 knock-in as well as cluster knock-out and over-expression strains were used to localize cluster miRNA expression as well as explore their functions. The adult head fat body is a major site of expression, and feeding behavior, innate immunity, metabolism, and perhaps stress responses are under cluster miRNA regulation. The feeding behavior results indicate that there is a feedback circuit between feeding time and cluster miRNA function as well as a surprising role of post-transcriptional regulation in these behaviors and physiology. Six samples of small RNA libraries (RNA size 19 to 29 nucleotides long) were prepared from Drosophila heads, each collected at one circadian time point during a light-dark cycle (ZT0, ZT4, ZT8, ZT12, ZT16, ZT20).
Project description:Objective: The early consumption of calorie-rich diet disrupts circadian rhythms and has adverse effects on memory, yet the effects of timerestricted feeding (TRF) and the underlying molecular mechanisms are unknown. Here, we set out to identify the behavioral and molecular circadian rhythms disruptions generated by juvenile obesogenic diet consumption and their restoration by TRF in male mice. Methods: Metabolic rhythms were measured by indirect calorimetry and memory performances by behavioral tasks. Hippocampal translatome (pS6_TRAP), enrichment and co-regulated gene network analyses were conducted to identify the molecular pathways involved in memory impairments and their restoration by TRF. Differential exon usage analyses, mass spectrometry and pharmacological intervention were used to confirm thyroid hormone signaling involvement. Results: We show that four weeks of TRF restore the rhythmicity of metabolic parameters and prevents memory impairments in mice fed a high fat-high sucrose (HFS) diet since weaning, independently of body fat levels. Hippocampal translatome and differential exon usage analyses indicate that impaired memory of mice under ad libitum HFS diet is accompanied by reduced thyroid hormone signaling and altered expression of astrocytic genes regulating glutamate neurotransmission. TRF restored the diurnal expression variation of part of these genes and intrahippocampal infusion of T3, the active form of thyroid hormone, rescues memory performances and astrocytic gene expression of ad libitum HFS diet-fed mice. Conclusions: Thus, thyroid hormones contribute to the TRF positive effects on both metabolism and memory in mice fed an obesogenic diet, highlighting this nutritional approach as a powerful tool in addressing obesity brain comorbidities and paving the way for further mechanistic studies on hippocampal thyroid signaling.
Project description:Restricted feeding impacts the hepatic circadian clock of WT mice. Cry1, Cry2 double KO mice lack a circadian clock and are thus expected to show rhythmical gene expression in the liver. Imposing a temporally restricted feeding schedule on these mice shows how the hepatic circadian clock and rhythmic food intake regulate rhythmic transcription in parallel Cry1, Cry2 double KO mice were entrained either to ad libitum or temporally restricted feeding (tRF) schedules. Food was made available to mice under the tRF regimen only between ZT(CT)1 and ZT(CT)9. Mice were then released into constant darkness while the respective feeding schedules were still maintained. Liver tissue was collected on the second day of constant darkness at the indicated timepoints. Total RNA was extracted and 5ug of RNA was used in the standard Affymetrix protocol for amplification, labeling and hybridization
Project description: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. While 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 wild-type and 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 genes expression, Bmal1 deletion having surprisingly more impact at the post-transcriptional level. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5â-TOP sequences and for genes involved in mitochondrial activity and harboring a TISU motif. The increased translation efficiency of 5â-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion impacts also 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. RNA-Seq from total RNA of mouse liver during the dirunal cycle. Time-series mRNA profiles of wild type (WT) and Bmal -/- mice under ad libitum and night restriced feeding regimen were generated by deep sequencing.
Project description:mRNA sequencing was used to identify genome wide transcriptional changes occuring in fly heads in response to spermidine feeding. This study shed light on the molecular mechanisms through wich spermidine can protect against age-dependent memory impairment. mRNA profiles from 3 and 10 day old Drosophila melanogaster heads were generated in duplicate by deep sequencing using Illumina GAIIx. mRNA profiles from flies that were fed food with 5mM spermidine were compared to profiles from flies that had no spermidine in thier food.
Project description:This SuperSeries is composed of the following subset Series: GSE40894: The Oscillating miRNA 959-964 cluster impacts Drosophila feeding time and other circadian outputs [expression]. GSE40943: The Oscillating miRNA 959-964 cluster impacts Drosophila feeding time and other circadian outputs [miRNA-seq]. Refer to individual Series