title: Interaction between sleep and metabolism in Drosophila with altered octopamine signaling.
abstract: Sleep length and metabolic dysfunction are correlated, but the causal relationship between these processes is unclear. Octopamine promotes wakefulness in the fly by acting through the insulin-producing cells (IPCs) in the fly brain. To determine if insulin signaling mediates the effects of octopamine on sleep:wake behavior, we assayed flies in which insulin signaling activity was genetically altered. We found that increasing insulin signaling does not promote wake, nor does insulin appear to mediate the wake-promoting effects of octopamine. Octopamine also affects metabolism in invertebrate species, including, as we show here, Drosophila melanogaster. Triglycerides are decreased in mutants with compromised octopamine signaling and elevated in flies with increased activity of octopaminergic neurons. Interestingly, this effect is mediated at least partially by insulin, suggesting that effects of octopamine on metabolism are independent of its effects on sleep. We further investigated the relative contribution of metabolic and sleep phenotypes to the starvation response of flies with altered octopamine signaling. Hyperactivity (indicative of foraging) induced by starvation was elevated in octopamine receptor mutants, despite their high propensity for sleep, indicating that their metabolic state dictates their behavioral response under these conditions. Moreover, flies with increased octopamine signaling do not suppress sleep in response to starvation, even though they are normally hyper-aroused, most likely because of their high triglyceride levels. Together, these data suggest that observed correlations between sleep and metabolic phenotypes can result from shared molecular pathways rather than causality, and environmental conditions can lead to the dominance of one phenotype over the other.
authors: Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors: Renske
authors: R
authors: Erion
authors: Justin R
authors: JR
authors: DiAngelo
authors: Amanda
authors: A
authors: Crocker
authors: Amita
authors: A
authors: Sehgal
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009655:Octopamine / Q000235:genetics / Q000378:metabolism*; D017982:Receptors, Biogenic Amine / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D012890:Sleep / Q000502:physiology*; D014280:Triglycerides / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D007328:Insulin; D017982:Receptors, Biogenic Amine; D014280:Triglycerides; C027604:norsynephrine receptor; D009655:Octopamine