TY - JOUR
T1 - Time-restricted feeding prevents deleterious metabolic effects of circadian disruption through epigenetic control of β cell function
AU - Brown, Matthew R.
AU - Sen, Satish K.
AU - Mazzone, Amelia
AU - Her, Tracy K.
AU - Xiong, Yuning
AU - Lee, Jeong Heon
AU - Javeed, Naureen
AU - Colwell, Christopher S.
AU - Rakshit, Kuntol
AU - LeBrasseur, Nathan K.
AU - Gaspar-Maia, Alexandre
AU - Ordog, Tamas
AU - Matveyenko, Aleksey V.
N1 - Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved.
PY - 2021/12
Y1 - 2021/12
N2 - 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 T2DM.
AB - 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 T2DM.
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U2 - 10.1126/sciadv.abg6856
DO - 10.1126/sciadv.abg6856
M3 - Article
C2 - 34910509
AN - SCOPUS:85122020161
SN - 2375-2548
VL - 7
JO - Science Advances
JF - Science Advances
IS - 51
M1 - eabg6856
ER -