Journal article
Transcriptional Basis for Rhythmic Control of Hunger and Metabolism within the AgRP Neuron
Cell metabolism, Vol.29(5), pp.1078-1091.e5
05/07/2019
DOI: 10.1016/j.cmet.2019.01.023
PMCID: PMC6506361
PMID: 30827863
Abstract
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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•The hypothalamic clock network aligns hunger and metabolism with sleep and wakefulness•The AgRP neuron clock remodels transcription in response to energy state•AgRP RiboTag profiling uncovers post-transcriptional control of bioenergetics•The transcriptional response to leptin requires an intact molecular clock
The central molecular clock aligns feeding with the sleep/wake state. Cedernaes et al. employ RNA sequencing in AgRP neurons across different nutrient states, revealing time-of-day-dependent enrichment of circadian and bioenergetic gene networks. They discover that the behavioral and transcriptional response to leptin varies from morning to evening, as the AgRP clock coordinates the leptin response and glucose metabolism with arousal.
Details
- Title: Subtitle
- Transcriptional Basis for Rhythmic Control of Hunger and Metabolism within the AgRP Neuron
- Creators
- Jonathan Cedernaes - Northwestern UniversityWenyu Huang - Northwestern UniversityKathryn Moynihan Ramsey - Northwestern UniversityNathan Waldeck - Northwestern UniversityLei Cheng - Northwestern UniversityBiliana Marcheva - Northwestern UniversityChiaki Omura - Northwestern UniversityYumiko Kobayashi - Northwestern UniversityClara Bien Peek - Northwestern UniversityDaniel C. Levine - Northwestern UniversityRavindra Dhir - University of PennsylvaniaRaj Awatramani - Northwestern UniversityChristopher A. Bradfield - University of Wisconsin–MadisonXiaozhong A. Wang - Northwestern UniversityJoseph S. Takahashi - Department of Neuroscience and Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390, USAMohamad Mokadem - University of IowaRexford S. Ahima - Johns Hopkins MedicineJoseph Bass - Northwestern University
- Resource Type
- Journal article
- Publication Details
- Cell metabolism, Vol.29(5), pp.1078-1091.e5
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cmet.2019.01.023
- PMID
- 30827863
- PMCID
- PMC6506361
- ISSN
- 1550-4131
- eISSN
- 1932-7420
- Grant note
- DOI: 10.13039/100000062, name: National Institute of Diabetes and Digestive and Kidney Diseases, award: R01DK090625, R01DK113011, R01DK100814, P01DK049210, K01DK105137-02; DOI: 10.13039/100000049, name: National Institute on Aging, award: P01AG011412; DOI: 10.13039/100000025, name: National Institute of Mental Health, award: R01MH110556; DOI: 10.13039/100007800, name: Diabetes Research and Training Center, award: P60DK020595; DOI: 10.13039/501100004359, name: Swedish Research Council, award: 2014-6888; DOI: 10.13039/501100003748, name: Swedish Society for Medical Research; DOI: 10.13039/501100003792, name: Swedish Brain Foundation; DOI: 10.13039/100000054, name: NCI, award: CA060553
- Language
- English
- Date published
- 05/07/2019
- Academic Unit
- Gastroenterology and Hepatology; Internal Medicine
- Record Identifier
- 9984359687402771
Metrics
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