Highlights Sleep is associated with fat mobilization and low ATP levels Metabolic regulation of sleep requires the SIK homolog KIN-29 KIN-29 acts in sensory neurons upstream of sleep-promoting neurons KIN-29 acts via the histone deacetylase HDA-4 in the metabolic regulation of sleep Liberation of energy from fat-storage cells promotes sleep. Combined Manuscript File 2 SUMMARY (146 words) Mechanisms underlying integration of sleep and energy homeostasis are largely unknown. We find that during Caenorhabditis elegans sleep, which is associated with energetically-expensive tasks, fat stores are depleted. Mutants lacking KIN-29, the C. elegans homolog of a mammalian Salt-Inducible Kinase (SIK) that signals sleep pressure, have defective sleep. They also have low cellular ATP levels despite high fat stores, indicating a defect in responding to cellular energy deficits. Liberating energy stores by overexpressing a lipase gene corrects adiposity and behavioral defects of kin-29 mutants. kin-29 acts in sensory neurons upstream of central sleep-controlling neurons. Removing the histone deacetylase hda-4 corrects the kin-29 mutant's sleep defects, suggesting that KIN-29 acts via HDA-4 to regulate sleep. We propose that KIN-29/SIK transduces low cellular energy charge into the mobilization of energy stores from adipocytes, which in turn promotes sleep. SIKs are therefore key nodes integrating sleep and energy homeostasis.
CITATION STYLE
Grubbs, J. J., Lopes, L. L., van der Linden, A. M., & Raizen, D. M. (2019). 0028 SIK-HDAC4 Signaling Is Required For The Metabolic Regulation Of Sleep. Sleep, 42(Supplement_1), A11–A11. https://doi.org/10.1093/sleep/zsz067.027
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