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

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.