GSE182936
Time-restricted feeding prevents deleterious metabolic effects of circadian disruption through epigenetic control of ß-cell function [ATACseq]
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 ß-cell function and loss of circadian ß-cell transcriptional and epigenetic control. In contrast, restoration of fasting/feeding cycle prevented CD-mediated metabolic dysfunction by reestablishing circadian regulation of glucose tolerance, ß-cell function, ß-cell transcriptional profile, and reestablishment of proline and acidic amino acid-rich basic leucine zipper (PAR-bZIP) transcription factor activity in ß-cells. This study provides mechanistic insights into beneficial effects of tRF and its role in prevention of ß-cell failure in T2DM. Overall design: Examination of open chromatin regions at circadian time 4 and 16 in pancreatic islets in mice exposed to either control, circadian disruption, or circadian disruption plus 8h time-restricted feeding