The clock gene cycle synchronizes circadian metabolic oscillations uniquely in reproductively active Culex pipiens females

Abstract The circadian clock regulates changes in daily metabolite abundance, coordinating animal activity, feeding and rest. The Northern house mosquito, Culex pipiens , also displays seasonal changes between periods of reproductive activity and overwintering diapause, regulated by changes in daylength. However, differences in metabolic oscillations between diapause and non-diapause have yet to be characterized. We hypothesized that reproductively active, non-diapausing mosquitoes would show large metabolic oscillations compared to diapausing mosquitoes. Our previous work demonstrated that CYCLE regulates insulin signaling, reproductive growth and olfaction, and that knocking out cycle causes a diapause-like state regardless of photoperiod, thus we predicted large-scale disruptions to the daily and seasonal metabolomes of CpCyc −/− mosquitoes. We identified 27 metabolites showing highly synchronized oscillations in non-diapausing wildtype (WT) females, but only 11 oscillating metabolites in WT diapausing females. We also observed large-scale metabolic disruptions in CpCyc −/− females reared under both long and short days, especially a loss of synchronicity between oscillations. This is the first report on differences in oscillating metabolites between diapausing and non-diapausing Cx. pipiens , and the impact of cycle on oscillating metabolites. This provides additional mechanistic insights as to how the circadian clock regulates daily and seasonal metabolic differences, with implications for insulin dysregulation and metabolic disorders.