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Status |
Public on Nov 24, 2021 |
Title |
Time-restricted feeding prevents deleterious metabolic effects of circadian disruption through epigenetic control of β-cell function [RNAseq] |
Organisms |
Mus musculus; Rattus norvegicus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
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.
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Overall design |
Examination of gene expression in: (1) Pancreatic islets from mice exposed to either control, circadian disruption, or circadian disruption plus 8h time-restricted feeding; (2) INS-1 832/13 cells transfected with scramble or Dbp siRNA
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Contributor(s) |
Brown MR, Sen SK, Mazzone A, Her TK, Xiong Y, Lee J, Javeed N, Colwell CS, Rakshit K, Lebrasseur NK, Gaspar-Maia A, Ordog T, Matveyenko AV |
Citation(s) |
34910509 |
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Submission date |
Aug 27, 2021 |
Last update date |
Feb 23, 2022 |
Contact name |
Matthew R Brown |
E-mail(s) |
brownm@broadinstitute.org
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Organization name |
Broad Institute
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Street address |
75 Ames St
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City |
Cambridge |
State/province |
MA |
ZIP/Postal code |
02142 |
Country |
USA |
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Platforms (2) |
GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
GPL22396 |
Illumina HiSeq 4000 (Rattus norvegicus) |
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Samples (42)
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This SubSeries is part of SuperSeries: |
GSE182938 |
Time-restricted feeding prevents deleterious metabolic effects of circadian disruption through epigenetic control of β-cell function |
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Relations |
BioProject |
PRJNA758375 |
SRA |
SRP334470 |