Misaligned feeding uncouples daily rhythms within brown adipose tissue and between peripheral clocks

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. • Restricting feeding window to 6 h leads to voluntary caloric restriction in mice • Daytime feeding in nocturnal mice leads to a misalignment between peripheral clocks • BAT’s core clock genes remain synchronized to the light/dark cycle despite misaligned feeding • Feeding time can uncouple nutrient- and clock-driven rhythmic genes in BAT Acosta-Rodríguez et al. reveal that daytime feeding in nocturnal mice decouples nutrient- and clock-driven rhythmic genes in BAT. Understanding tissue-specific responses to environmental cues may help elucidate how dietary interventions influence well-being. These findings stress the importance of considering intervention and sampling time to evaluate physiology.