Misaligned feeding uncouples daily rhythms within brown adipose tissue and between peripheral clocks
Victoria A. Acosta-Rodríguez,
Filipa Rijo-Ferreira,
Laura van Rosmalen,
Mariko Izumo,
Noheon Park,
Chryshanthi Joseph,
Chelsea Hepler,
Anneke K. Thorne,
Jeremy Stubblefield,
Joseph Bass,
Carla B. Green,
Joseph S. Takahashi
Affiliations
Victoria A. Acosta-Rodríguez
Department of Neuroscience, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA; Corresponding author
Filipa Rijo-Ferreira
Department of Neuroscience, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA; Berkeley Public Health, Molecular Cell Biology Department, University of California, Berkeley, Berkeley, CA, USA
Laura van Rosmalen
Department of Neuroscience, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA; The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Mariko Izumo
Department of Neuroscience, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA
Noheon Park
Department of Neuroscience, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA
Chryshanthi Joseph
Department of Neuroscience, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA
Chelsea Hepler
Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Anneke K. Thorne
Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Jeremy Stubblefield
Department of Neuroscience, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA; Benedictine College, Atchison, KS, USA
Joseph Bass
Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Carla B. Green
Department of Neuroscience, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA; Corresponding author
Joseph S. Takahashi
Department of Neuroscience, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA; Corresponding author
Summary: Extended food consumption during the rest period perturbs the phase relationship between circadian clocks in the periphery and the brain, leading to adverse health effects. Beyond the liver, how metabolic organs respond to a timed hypocaloric diet is largely unexplored. We investigated how feeding schedules impacted circadian gene expression in epididymal white and brown adipose tissue (eWAT and BAT) compared to the liver and hypothalamus. We restricted food to either daytime or nighttime in C57BL/6J male mice, with or without caloric restriction. Unlike the liver and eWAT, rhythmic clock genes in the BAT remained insensitive to feeding time, similar to the hypothalamus. We uncovered an internal split within the BAT in response to conflicting environmental cues, displaying inverted oscillations on a subset of metabolic genes without modifying its local core circadian machinery. Integrating tissue-specific responses on circadian transcriptional networks with metabolic outcomes may help elucidate the mechanism underlying the health burden of eating at unusual times.
