Regulation of Metabolic Rhythms by Glial Clocks

Rhythmicity is a central feature of behavioral and physiological processes, including sleep, immune responses, and metabolism. Research on brain control of these processes has largely focused on neurons, with less known about the role of clock genes in glial cells. In this study, we addressed the function of glial clocks by targeting the expression of key clock genes in glia of Drosophila melanogaster. Loss of the period (per) gene in glia increases sleep following aseptic injury and loss of either per or timeless (tim) significantly reduces locomotor activity in light:dark cycles and in constant dark, but other than this, the major effect of clock gene loss in glia is on metabolic function. We demonstrate that disruption of either tim or per in glia affects glycogen stores and reduces metabolic rate. Disruption of either tim or per in glia also affects rhythms of feeding and overall food consumption. Notably, these effects of clock disruption are mediated by distinct glial subtypes, especially cortex glia. We propose that the major role of glial clocks is in the control of energy homeostasis and metabolic rhythms, which likely also accounts for effects on locomotor activity. These findings link metabolism and behavior via circadian regulation in glia.