Down-regulation of a cytokine secreted from peripheral fat bodies improves visual attention while reducing sleep in Drosophila

Abstract

Sleep is vital for survival. Yet under environmentally challenging conditions, such as starvation, animals suppress their need for sleep. Interestingly, starvation-induced sleep loss does not evoke a subsequent sleep rebound. Little is known about how starvation-induced sleep deprivation differs from other types of sleep loss, or why some sleep functions become dispensable during starvation. Here, we demonstrate that down-regulation of the secreted cytokine unpaired 2 ( upd2 ) in Drosophila flies may mimic a starved-like state. We used a genetic knockdown strategy to investigate the consequences of upd2 on visual attention and sleep in otherwise well-fed flies, thereby sidestepping the negative side effects of undernourishment. We find that knockdown of upd2 in the fat body (FB) is sufficient to suppress sleep and promote feeding-related behaviors while also improving selective visual attention. Furthermore, we show that this peripheral signal is integrated in the fly brain via insulin-expressing cells. Together, these findings identify a role for peripheral tissue-to-brain interactions in the simultaneous regulation of sleep quality and attention, to potentially promote adaptive behaviors necessary for survival in hungry animals.

A screen for sleep and starvation resistance identifies a wake-promoting role for the auxiliary channel unc79

“…Here, we screened by targeting gene function ubiquitously to identify regulators of sleep and metabolic function. Growing evidence suggests sleep is regulated by complex interactions between the brain and periphery, including the findings that mutants impacting fat storage, and communication from the fat body to the brain significantly impact sleep (Thimgan et al 2010;Slocumb et al 2015;Ertekin et al 2020).…”

“…The study of sleep in flies has predominantly focused on the role of genes and neurons under fed conditions, leading to the identification of many distinct circuits that promote sleep and wakefulness (Allada and Siegel 2008;Sehgal and Mignot 2011;Ly et al 2018). There is growing evidence that additional cell types are critical regulators of sleep including multiple classes of glia, endocrine cells, and the fat body (A rtiushin et al 2018;Stahl et al 2018;Vanderheyden et al 2018;Yurgel et al 2018;Ertekin et al 2020).…”

A screen for sleep and starvation resistance identifies a wake-promoting role for the auxiliary channel unc79

“…Here, we screened by targeting gene function ubiquitously to identify regulators of sleep and metabolic function. Growing evidence suggests sleep is regulated by complex interactions between the brain and periphery, including the findings that mutants impacting fat storage, and communication from the fat body to the brain significantly impact sleep ( Thimgan et al 2010 ; Slocumb et al 2015 ; Ertekin et al 2020 ).…”

“…The study of sleep in flies has predominantly focused on the role of genes and neurons under fed conditions, leading to the identification of many distinct circuits that promote sleep and wakefulness ( Allada and Siegel 2008 ; Sehgal and Mignot 2011 ; Ly et al 2018 ). There is growing evidence that additional cell types are critical regulators of sleep including multiple classes of glia, endocrine cells, and the fat body ( Artiushin et al 2018 ; Stahl et al 2018 ; Vanderheyden et al 2018 ; Yurgel et al 2018 ; Ertekin et al 2020 ). Furthermore, the genes and neurons regulating sleep can differ based on environmental context ( Griffith 2013 ; Beckwith and French 2019 ; Shafer and Keene 2021 ).…”

Nuclear Retention of Leptin/Upd2 Regulates Organismal Resilience to Nutrient Extremes

“…Leptin in mammals (Ahima et al, 1996;Farooqi and O'Rahilly, 2009) and its functional ortholog in fruit-flies, Unpaired2 (Upd2) (Rajan and Perrimon, 2012), are primary adipokines that are released in proportion to fat stores (Hickey et al, 1996;Kolaczynski et al, 1996a;Kolaczynski et al, 1996b). Both in flies and mammals, Leptin/Upd2 impinges on brain circuits that control energy expenditure, appetite, and overall metabolism (Brent and Rajan, 2020;Ertekin et al, 2020;Friedman and Halaas, 1998;Rajan and Perrimon, 2012).…”