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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 [ChIPseq] |
| Organism |
Rattus norvegicus |
| Experiment type |
Genome binding/occupancy 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 DBP binding in INS1 832/13 pancreatic beta cells
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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 (1) |
| GPL25029 |
NextSeq 550 (Rattus norvegicus) |
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| Samples (2) |
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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 |
PRJNA758377 |
| SRA |
SRP334472 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE182933_RAW.tar |
818.2 Mb |
(http)(custom) |
TAR (of BED, BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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