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: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: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:To further character the significant changes in renal gene expression after time restricted feeding (TRF) treatment in CKD mice,RNA-sequencing was performed in the kidneys.
Project description:The integration of circadian and metabolic signals is essential for maintaining robust circadian rhythms and ensuring efficient metabolism and energy use. Using Drosophila as an animal model, we showed observed strong correlation between daily daily rhythms of protein O-linked N-acetylglucosaminylation (O-GlcNAcylation) and clock-controlled feeding-fasting cycles, suggesting that O-GlcNAcylation rhythms are primarily driven by nutrient input. Interestingly, daily O-GlcNAcylation rhythms were severely dampened when we subjected flies to time-restricted feeding (TRF) at unnatural feeding time. This suggests the presence of a clock-regulated buffering mechanism that prevents excessive O-GlcNAcylation at non-optimal times of the day-night cycle, which could disrupt circadian health. We performed targeted metabolomic analysis on hexosamine biosynthetic pathway (HBP), which produces UDP-GlcNAc (the substrate for O-GlcNAcylation), to evaluate the daily activity of HBP enzymes under TRF conditions. We found glutamine--fructose-6-phosphate amidotransferase (GFAT) mediates this buffering mechanism.
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:Increased susceptibility of circadian clock mutant mice to metabolic diseases has led to the understanding that a molecular circadian clock is necessary for metabolic homeostasis. Circadian clock produces a daily rhythm in activity-rest and an associated rhythm in feeding-fasting. Feeding-fasting driven programs and cell autonomous circadian oscillator act synergistically in the liver to orchestrate daily rhythm in metabolism. However, an imposed feeding-fasting rhythm, as in time-restricted feeding, can drive some rhythm in liver gene expression in clock mutant mice. We tested if TRF alone, in the absence of a circadian clock in the liver or in the whole animal can prevent obesity and metabolic syndrome. Mice lacking the clock component Bmal1 in the liver, Rev-erb alpha/beta in the liver or cry1-/-;cry2-/- (CDKO) mice rapidly gain weight and show genotype specific increased susceptibility to dyslipidemia, hypercholesterolemia and glucose intolerance under ad lib fed condition. However, when the mice were fed the same diet under time-restricted feeding regimen that imposed 10 h feeding during the night, they were protected from weight gain and other metabolic diseases. Transcriptome and metabolome analyses of the liver from there mutant mice showed TRF reduces de novo lipogenesis, increased beta-oxidation independent of a circadian clock. TRF also enhanced cellular defense to metabolic stress. These results suggest a major function of the circadian clock in metabolic homeostasis is to sustain a daily rhythm in feeding and fasting. The feeding-fasting cycle orchestrates a balance between nutrient stress and cellular response to maintain homeostasis.
Project description:Feeding resveratrol to Drosophila melanogaster extends lifespan. Studies of microarray show similarities between calorie/dietary restriction and resveratrol on both a gene expression and biological pathway level. 9 samples: 3 biological replicates each of normal diet, restricted diet and normal diet plus resveratrol