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Publication : Transcriptional Basis for Rhythmic Control of Hunger and Metabolism within the AgRP Neuron.

First Author  Cedernaes J Year  2019
Journal  Cell Metab Volume  29
Issue  5 Pages  1078-1091.e5
PubMed ID  30827863 Mgi Jnum  J:274943
Mgi Id  MGI:6303422 Doi  10.1016/j.cmet.2019.01.023
Citation  Cedernaes J, et al. (2019) Transcriptional Basis for Rhythmic Control of Hunger and Metabolism within the AgRP Neuron. Cell Metab 29(5):1078-1091.e5
abstractText  The 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 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 response to leptin. Our results reveal that time-of-day restriction in transcriptional control of energy-sensing neurons underlies the alignment of hunger and food acquisition with the sleep/wake state.
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