Sleep-dependent modulation of metabolic rate inDrosophila

Abstract

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 sleepdependent 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 CO 2 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.Keywords: Drosophila, metabolism, respirometry, calorimetry, sleep . CC-BY 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/124198 doi: bioRxiv preprint first posted online Apr. 4, 2017; 3 Significance 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.. CC-BY 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

Dietary fatty acids promote sleep through a taste‐independent mechanism

“…The effects of diet on sleep are complex and it is likely that the effects diet differs depending on genetic background, availability of nutrients during development and age . Previous work has shown that flies fed a diet of sugar alone sleep more than starved flies, suggesting that sugar promotes sleep . While we previously reported that sleep does not differ in flies fed a diet of 5% sucrose or standard fly food, here we find that the phenotype of sucrose is intermediate between agar and standard fly food.…”

“…Flies display all the behavioral hallmarks of sleep, including prolonged immobility, elevated arousal threshold and rebound following sleep deprivation . Recent work has identified behavioral, electrophysiological and metabolic states that associate with light and deeper sleep, suggesting distinguishable sleep stages are also present in fruit flies . In addition, genetic analyses suggest the molecular and neural circuit principles regulating sleep, as well as the functional effects of sleep loss, are highly conserved between flies and mammals .…”

Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut

“…We do not think that this is a major factor behind the observed phenomena because sleep is not merely a period of immobility. Metabolic changes associated with normal daily sleep-wake cycles are separable from changes in locomotion (Bonnet et al, 1991;Stahl et al, 2017), and increased locomotion by itself does not seem to contribute significantly to the increased metabolic rate and energy expenditure during experimental sleep deprivation (Barf et al, 2012;Bergmann et al, 1989;Caron and Stephenson, 2010). Additionally, intense physical activity increases the levels of ROS in muscles (Powers and Jackson, 2008), but we did not detect changes in this tissue, suggesting that our observations do not stem simply from physical exhaustion.…”

“…The vast majority of ROS ($90%) are generated during mitochondrial oxygen-dependent ATP synthesis (Balaban et al, 2005), making this organelle an obvious candidate for the relevant ROS source. Metabolism increases during sleep disruption (Barf et al, 2012;Bonnet et al, 1991;Caron and Stephenson, 2010;Everson et al, 1989;Everson and Wehr, 1993;Stahl et al, 2017;Valenti et al, 2017), and metabolic regulation may have been an original sleep function. The concentration of atmospheric oxygen changed significantly several times in Earth's history, which is thought to have led to eukaryotic and multicellular life (El Albani et al, 2010;Sessions et al, 2009).…”

Energy Deficit is a Key Driver of Sleep Homeostasis

“…Sleep and eating-typically mutually exclusive behaviors that are amongst those most vital for survival and prosperity-are intricately linked. Food deprivation increases activity levels in many species, including flies 3 , whereas food ingestion temporarily elevates immediate sleepiness-a phenomenon colloquially known as "food coma"-in flies 4 , laboratory rodents 5,6 , and humans 7,8 . Conversely, acute and chronic sleep deprivation is associated with altered taste perception, food cravings, increased appetite and food intake, rapid weight gain, and detrimental metabolic changes in laboratory rodents 9 and humans 10 .…”