期刊
CELL METABOLISM
卷 29, 期 5, 页码 1078-+出版社
CELL PRESS
DOI: 10.1016/j.cmet.2019.01.023
关键词
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资金
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01DK090625, R01DK113011, R01DK100814, P01DK049210]
- National Institute on Aging [P01AG011412]
- National Institute of Mental Health [R01MH110556]
- Chicago Biomedical Consortium [S-007]
- University of Chicago Diabetes Research and Training Center grant [P60DK020595]
- NIDDK [K01DK105137-02]
- Swedish Research Council [2014-6888]
- Swedish Society for Medical Research
- Swedish Brain Foundation
- Northwestern University RHLCCC Flow Cytometry Facility [NCI CA060553]
- Cancer Center Support Grant [NCI CA060553]
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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