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.