Circadian-clock independent ultradian rhythms in lipid metabolism in Drosophila fat body

The role of circadian clocks in regulating metabolic processes has been studied extensively. Yet, the physiological impacts of the circadian system on metabolic states across species and life stages remain to be explored. This study investigates the relationship between circadian rhythms and metabolic regulation in the fat body of Drosophila larva, an organ crucial for maintaining metabolic homeostasis, growth, and developmental timing. Larval fat body is analogous to the mammalian liver and adipose tissue but lacks a canonical circadian clock. Around-the-clock RNA-sequencing analysis on the fat bodies of wild-type and period clock gene null mutant larvae revealed circadian rhythms in the transcriptome of wild-type larvae. Surprisingly, period mutants exhibited 12-h rhythms in the expression of numerous genes, particularly those involved in peroxisome function, lipid metabolism, and oxidative stress response. Consistent with these transcriptomic data, peroxisome biogenesis,s and activity demonstrated 12-h rhythms in period mutant fat bodies. Furthermore, levels of reactive oxygen species displayed inverse-phased rhythms to that of lipid peroxidation, with 24-h rhythms in wild-type and 12-h rhythms in period mutant fat bodies. Moreover, while daily fat storage levels in wild-type larvae remained constant, period mutants exhibited fluctuations with a 12-h period and a net reduction in body fat storage. Collectively, our results identified clock-independent ultradian rhythms in lipid metabolism, which may contribute to maintaining the metabolic, energetic, and redox homeostasis essential for larval survival and development.