Altered Metabolism during the Dark Period in Drosophila Short Sleep Mutants

Sleep
is regulated via circadian mechanisms, but effects of sleep
disruption on physiological rhythms, in particular metabolic cycling,
remain unclear. To examine this question, we probed diurnal metabolic
alterations of two Drosophila short sleep mutants, fumin and sleepless. Samples were collected
with high temporal sampling (every 2 h) over 24 h under a 12:12 light:dark
cycle, and profiling was done using an ion-switching LCMS/MS method.
Fewer metabolites with 24 h oscillations were noted with short sleep
(50 and 46 in fumin and sleepless, BH. Q < 0.2 by RAIN analysis) compared to a
wild-type control (iso31, 63 with BH. Q < 0.2), and peak phases of the sleep mutants were consolidated
into two major phase peaks at mid-day and middle of night. Overall,
altered nicotinate/nicotinamide, alanine/aspartate/glutamate, acetylcholine,
glyoxylate/dicarboxylate, and TCA cycle metabolism were observed in
the short sleep mutants, indicative of increased energetic demand
and oxidative stress compared to wild type. Both changes in cycling
and discriminant models suggest unique alterations in the dark period
indicative of constrained metabolic networks. Thus, we conclude that
sleep loss alters metabolic function uniquely throughout the day,
and further examination of specific mechanisms is warranted.