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

ABSTRACT: [Figure: see text].

SUBMITTER: Brown MR

PROVIDER: S-EPMC8673777 | biostudies-literature |

REPOSITORIES: biostudies-literature

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-11-24 | GSE182938 | GEO

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.

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

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

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

Project description:Time-restricted feeding prevents deleterious metabolic effects of circadian disruption through epigenetic control of β-cell function

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

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

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

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

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

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

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Time-Restricted Feeding Prevents Obesity and Metabolic Syndrome in Mice Lacking a Circadian Clock.

Project description:Increased susceptibility of circadian clock mutant mice to metabolic diseases has led to the idea that a molecular clock is necessary for metabolic homeostasis. However, these mice often lack a normal feeding-fasting cycle. We tested whether time-restricted feeding (TRF) could prevent obesity and metabolic syndrome in whole-body Cry1;Cry2 and in liver-specific Bmal1 and Rev-erb?/? knockout mice. When provided access to food ad libitum, these mice rapidly gained weight and showed genotype-specific metabolic defects. However, when fed the same diet under TRF (food access restricted to 10 hr during the dark phase) they were protected from excessive weight gain and metabolic diseases. Transcriptome and metabolome analyses showed that TRF reduced the accumulation of hepatic lipids and enhanced cellular defenses against metabolic stress. These results suggest that the circadian clock maintains metabolic homeostasis by sustaining daily rhythms in feeding and fasting and by maintaining balance between nutrient and cellular stress responses.

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