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Time-restricted feeding prevents deleterious metabolic effects of circadian disruption through epigenetic control of β-cell function [ChIPseq]

ABSTRACT: Circadian rhythm disruption (CD) is associated with dysregulation of glucose homeostasis and Type 2 diabetes mellitus (T2DM). While the link between CD and T2DM remains unclear, there is accumulating evidence that disruption of fasting/feeding cycles mediates CD-induced metabolic dysfunction. Herein we utilized an approach encompassing analysis of behavioral, physiological, transcriptomic, and single-cell epigenomic effects of CD and consequences of restoration of fasting/feeding cycles through time-restricted feeding (tRF) in mice. Results show that CD perturbs glucose homeostasis through disruption of pancreatic β-cell function and loss of circadian β-cell transcriptional and epigenetic control. In contrast, restoration of fasting/feeding cycle prevented CD-mediated metabolic dysfunction by reestablishing circadian regulation of glucose tolerance, β-cell function, β-cell transcriptional profile, and reestablishment of proline and acidic amino acid-rich basic leucine zipper (PAR-bZIP) transcription factor activity in β-cells. This study provides mechanistic insights into beneficial effects of tRF and its role in prevention of β-cell failure in T2DM.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE182933 | GEO | 2021/11/24

REPOSITORIES: GEO

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Time-restricted feeding prevents deleterious metabolic effects of circadian disruption through epigenetic control of β-cell function [ATACseq]

Project description:Circadian rhythm disruption (CD) is associated with dysregulation of glucose homeostasis and Type 2 diabetes mellitus (T2DM). While the link between CD and T2DM remains unclear, there is accumulating evidence that disruption of fasting/feeding cycles mediates CD-induced metabolic dysfunction. Herein we utilized an approach encompassing analysis of behavioral, physiological, transcriptomic, and single-cell epigenomic effects of CD and consequences of restoration of fasting/feeding cycles through time-restricted feeding (tRF) in mice. Results show that CD perturbs glucose homeostasis through disruption of pancreatic β-cell function and loss of circadian β-cell transcriptional and epigenetic control. In contrast, restoration of fasting/feeding cycle prevented CD-mediated metabolic dysfunction by reestablishing circadian regulation of glucose tolerance, β-cell function, β-cell transcriptional profile, and reestablishment of proline and acidic amino acid-rich basic leucine zipper (PAR-bZIP) transcription factor activity in β-cells. This study provides mechanistic insights into beneficial effects of tRF and its role in prevention of β-cell failure in T2DM.

2021-11-24 | GSE182936 | GEO

Time-restricted feeding prevents deleterious metabolic effects of circadian disruption through epigenetic control of β-cell function [RNAseq]

2021-11-24 | GSE182931 | GEO

Time-restricted feeding prevents deleterious metabolic effects of circadian disruption through epigenetic control of β-cell function [scATAC-seq]

2021-11-24 | GSE182937 | GEO

Hepatic transcriptome by Next Generation Sequencing of WT and clock mutant mice fed a HFD ad libitum or time-restricted feeding.

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.

2018-08-30 | GSE102072 | GEO

Bae2017 - Mathematical analysis of circadian disruption and metabolic re-entrainment of hepatic gluconeogenesis

Project description:The circadian rhythms influence the metabolic activity from molecular level to tissue, organ, and host level. Disruption of the circadian rhythms manifests to the host's health as metabolic syndromes, including obesity, diabetes, and elevated plasma glucose, eventually leading to cardiovascular diseases. Therefore, it is imperative to understand the mechanism behind the relationship between circadian rhythms and metabolism. To start answering this question, we propose a semimechanistic mathematical model to study the effect of circadian disruption on hepatic gluconeogenesis in humans. Our model takes the light-dark cycle and feeding-fasting cycle as two environmental inputs that entrain the metabolic activity in the liver. The model was validated by comparison with data from mice and rat experimental studies. Formal sensitivity and uncertainty analyses were conducted to elaborate on the driving forces for hepatic gluconeogenesis. Furthermore, simulating the impact of Clock gene knockout suggests that modification to the local pathways tied most closely to the feeding-fasting rhythms may be the most efficient way to restore the disrupted glucose metabolism in liver.

2021-04-08 | BIOMD0000001005 | BioModels

The effects of temporally restricted feeding on hepatic gene expression of Cry1, Cry2 double KO mice

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

2009-11-23 | E-GEOD-13062 | biostudies-arrayexpress

Diurnal transcriptome landscape of a multi-tissue response to time restricted feeding in mammals

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.

2022-12-20 | GSE190389 | GEO

Fasting Imparts a Switch to Alternative Circadian Transcriptional Pathways in Liver and Muscle

Project description:The circadian gene expression in peripheral tissue displays rhythmicity which is driven by the circadian clock and feeding-fasting cycle in mammals. In this study, circadian transcriptome was performed to investigate how fasting influences circadian gene regulation.

2018-12-18 | GSE107787 | GEO

Young and undamaged recombinant albumin alleviates T2DM by improving hepatic glycolysis through EGFR and protecting islet β cells in mice

Project description:Type 2 Diabetes Mellitus (T2DM) is a severe disease that has reached epidemic proportions. In this study, treatment of T2DM mice with young, undamaged, and ultrapure recombinant mouse serum albumin (rMSA) increased their serum albumin levels, which resulted in a reversal of the disease including reduced fasting blood glucose levels, improved glucose tolerance, increased glucose-stimulated insulin secretion, and alleviated islet atrophy. At the cellular level, rMSA improved glucose uptake and glycolysis in hepatocytes. Mechanistically, rMSA reduced the binding between CAV1 and EGFR to increase EGFR activation leading to PI3K-AKT activation. Furthermore, rMSA extracellularly reduced the rate of fatty acid uptake by islet β-cells, which relieved the accumulation of intracellular ceramide, endoplasmic reticulum stress, and apoptosis. This study provided the first clear demonstration that injections of young, undamaged, and ultrapure recombinant serum albumin can alleviate T2DM in mice.

2023-11-11 | GSE217975 | GEO

Effects of extensive fasting and subsequent feeding on hepatic transcription

Project description:Temporally restricted feeding has a profound effect on the circadian clock. Fasting and feeding paradigms are known to influence hepatic transcription. This dataset shows the dynamic effects of refeeding mice after a 24hour fasting period.

2009-11-23 | GSE13063 | GEO

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