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Transcriptional Basis for Rhythmic Control of Hunger and Metabolism within the AgRP Neuron
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine. Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.ORCID iD: 0000-0002-9052-8372
Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
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2019 (English)In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 29, no 5, p. 1078-1091.e5Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2019. Vol. 29, no 5, p. 1078-1091.e5
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-384072DOI: 10.1016/j.cmet.2019.01.023ISI: 000467054100010PubMedID: 30827863OAI: oai:DiVA.org:uu-384072DiVA, id: diva2:1318779
Funder
Swedish Research Council, 2014-6888
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2019-05-28 Created: 2019-05-28 Last updated: 2019-05-28Bibliographically approved

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