DiAngelo, J. | bioRxiv Science

bioRxiv2018

Ade2 functions in the Drosophila fat body to promote sleep

Metabolic state is a potent modulator of sleep and circadian behavior and animals acutely modulate their sleep in accordance with internal energy stores and food availability. Across phyla, hormones secreted from adipose tissue act in the brain to control neural physiology and behavior to modulate sleep and metabolic state. Growing evidence suggests the fat body is a critical regulator of complex behaviors, but little is known about the genes that function within the fat body to regulate sleep. To identify molecular factors functioning in the periphery to regulate sleep, we performed an RNAi screen selectively knocking down genes in the fat body. We found that knockdown of Phosphoribosylformylglycinamidine synthase/Pfas(Ade2), a highly conserved gene involved the biosynthesis of purines, reduces sleep and energy stores. Flies heterozygous for multiple Ade2 mutations are also short sleepers and this effect is partially rescued by restoring Ade2 to the fat body. Targeted knockdown of Ade2 in the fat body does not alter arousal threshold or the homeostatic response to sleep deprivation, suggesting a specific role in modulating baseline sleep duration. Together, these findings suggest Ade2 functions within the fat body to promote both sleep and energy storage, providing a functional link between these processes.

neuroscience↗

bioRxiv2017

Sleep-Dependent Modulation Of Metabolic Rate In Drosophila

Dysregulation of sleep is associated with metabolic diseases, and metabolic rate is acutely regulated by sleep-wake behavior. In humans and rodent models, sleep loss is associated with obesity, reduced metabolic rate, and negative energy balance, yet little is known about the neural mechanisms governing interactions between sleep and metabolism. We have developed a system to simultaneously measure sleep and metabolic rate in individual Drosophila, allowing for interrogation of neural systems governing interactions between sleep and metabolic rate. Like mammals, metabolic rate in flies is reduced during sleep and increased during sleep deprivation suggesting sleep-dependent regulation of metabolic rate is conserved across phyla. The reduction of metabolic rate during sleep is not simply a consequence of inactivity because metabolic rate is reduced [~]30 minutes following the onset of sleep, raising the possibility that CO2 production provides a metric to distinguish different sleep states in the fruit fly. To examine the relationship between sleep and metabolism, we determined basal and sleep-dependent changes in metabolic rate is reduced in starved flies, suggesting that starvation inhibits normal sleep-associated effects on metabolic rate. Further, translin mutant flies that fail to suppress sleep during starvation demonstrate a lower basal metabolic rate, but this rate was further reduced in response to starvation, revealing that regulation of starvation-induced changes in metabolic rate and sleep duration are genetically distinct. Therefore, this system provides the unique ability to simultaneously measure sleep and oxidative metabolism, providing novel insight into the physiological changes associated with sleep and wakefulness in the fruit fly.\n\nSignificance statementMetabolic disorders are associated with sleep disturbances, yet our understanding of the mechanisms underlying interactions between sleep and metabolism remain limited. Here, we describe a novel system to simultaneously record sleep and metabolic rate in single Drosophila. Our findings reveal that uninterrupted sleep bouts of 30 minutes or greater are associated with a reduction in metabolic rate providing a physiological readout of sleep. Use of this system, combined with existing genetic tools in Drosophila, will facilitate identification of novel sleep genes and neurons, with implications for understanding the relationship between sleep loss and metabolic disease.

neuroscience↗