Energy Deficit Is a Key Driver of Sleep Homeostasis

Sleep and feeding-typically mutually exclusive behaviors that are vital for survival and health-are intricately linked. Across species, chronic sleep loss or deprivation is associated with increased caloric intake, while fasting typically induces sleep suppression. Despite evidence for a dynamic relationship between these behaviors, how sleep affects eating habits and how changes in feeding behavior and nutrition alter sleep are not completely understood. Distinct neuronal manipulations in <i>Drosophila melanogaster</i> can dissociate sleep loss from subsequent homeostatic rebound, offering an optimal platform to examine the precise interplay between these fundamental behaviors. Here, we investigated concomitant changes in sleep and food intake in individual flies, as well as respiratory metabolic expenditure that accompany behavioral and neuronal manipulations that induce sleep loss in males. We find that sleep disruptions resulting in energy deficit through increased metabolic expenditure and manifesting as increased food intake were consistently followed by rebound sleep. In contrast, sleep loss that does not induce rebound sleep was not accompanied by increased metabolism and food intake. Our results suggest that homeostatic sleep rebound is linked to energy deficit accrued during sleep loss. Collectively, these findings support the notion that sleep functions to conserve energy and highlight the need to examine the effects of metabolic therapeutics on sleep. Our findings also stress the importance of precise measurements of sleep and the value of considering multiple indicators of energy balance, including metabolism and food intake.