GSE124693
Coordination of hunger and sleep through circadian regulation of transcription in energy-sensing neurons
Alignment of fasting and feeding with the sleep/wake cycle is coordinated by hypothalamic neurons, though the underlying molecular programs remain incompletely understood. Here we demonstrate that the clock transcription pathway maximizes eating during wakefulness and glucose production during sleep through transcription pathway maximizes eating during autonomous circadian regulation of NPY/AgRP neurons. Tandem profiling of whole cell and ribosome-bound mRNAs in morning and evening under dynamic fasting and fed conditions identified temporal control of activity-dependent gene repertoires in AgRP neurons central to synaptogenesis, bioenergetics, and neurotransmitter and peptidergic signaling. Synaptic and circadian pathways were specific to whole cell RNA analyses, while bioenergetic pathways were selectively enriched in the ribosome-bound transcriptome. Finally, we demonstrate that the AgRP clock mediates the transcriptional food acquisition with sleep/wake state. response to leptin. Our results reveal that time-of-day restriction in transcriptional control of energy-sensing neurons underlies the alignment of hunger and day restriction in transcriptional control of energy-sensing neurons underlies the alignment of hunger and food acquisition with sleep/wake state. Overall design: Examination of AGRP neurons including BMAL1-KO, under 3 different nutrient states, leptin adiministration, and time of day collection points.