Circadian Rhythms of Metabolite Abundance in Drosophila are Largely Driven by Time of Feeding

ABSTRACT: Organisms exhibit daily oscillations in metabolite abundance. These oscillations could arise from circadian clock control of metabolic pathways in peripheral tissues, or may be secondary to rhythmic food intake, which is primarily controlled by central circadian clocks in the brain. To determine the relative contribution of central and peripheral clocks and behavioral cycles to metabolic rhythms in the fruit fly, Drosophila melanogaster, we conducted large-scale metabolite profiling with fine temporal resolution across multiple days in control flies with intact molecular clocks and in flies where CRISPR/Cas9 gene editing was used to specifically eliminate molecular circadian clock function in the fat body, a peripheral metabolic tissue, or the brain. As these latter flies lack feeding rhythms due to central circadian clock dysfunction, we also included an experimental cohort of flies which lacked central brain clocks but were subjected to time-restricted feeding (TRF) protocols to impose feeding rhythms. Single-nuclei RNA sequencing confirmed selective molecular clock elimination following fat body manipulations, which was associated with predicted alterations in clock gene expression and an attenuation of time-of-day differences in the abundance of fat body transcripts involved in key metabolic pathways. Interestingly, we identified few rhythmically expressed metabolites in flies that were allowed ad libitum food access. In contrast, flies which lacked brain clocks but were raised on TRF exhibited robust circadian abundance rhythms across a large range of metabolites. These findings suggest that metabolic rhythms in Drosophila are more strongly regulated by feeding cycles than by direct circadian clock control of metabolic pathways despite the presence of metabolic genes that exhibit local-clock dependent modulation of expression across the day.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE334463 | GEO | 2026/06/22

REPOSITORIES: GEO