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

Circadian rhythm disruption (CD) is associated with impaired 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 metabolic dysfunction. Here, we used an approach...

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Detalles Bibliográficos
Autores principales: Brown, Matthew R., Sen, Satish K., Mazzone, Amelia, Her, Tracy K., Xiong, Yuning, Lee, Jeong-Heon, Javeed, Naureen, Colwell, Christopher S., Rakshit, Kuntol, LeBrasseur, Nathan K., Gaspar-Maia, Alexandre, Ordog, Tamas, Matveyenko, Aleksey V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8673777/
https://www.ncbi.nlm.nih.gov/pubmed/34910509
http://dx.doi.org/10.1126/sciadv.abg6856
Descripción
Sumario:Circadian rhythm disruption (CD) is associated with impaired 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 metabolic dysfunction. Here, we used an approach encompassing analysis of behavioral, physiological, transcriptomic, and epigenomic effects of CD and consequences of restoring 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 transcriptional and epigenetic identity. In contrast, restoration of fasting/feeding cycle prevented CD-mediated dysfunction by reestablishing circadian regulation of glucose tolerance, β cell function, transcriptional profile, and reestablishment of proline and acidic amino acid–rich basic leucine zipper (PAR bZIP) transcription factor DBP expression/activity. This study provides mechanistic insights into circadian regulation of β cell function and corresponding beneficial effects of tRF in prevention of β T2DM.