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

ABSTRACT: 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 mutant 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 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 a clock-independent ultradian rhythms in lipid metabolism, which may contribute to maintaining the metabolic, energetic, and redox homeostasis essential for larval survival and development.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE282559 | GEO | 2024/12/19

REPOSITORIES: GEO

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			Action	DRS
		Other
	GSE282559_CT.counts_P.csv.gz	Csv
	GSE282559_CT.counts_W.csv.gz	Csv
	GSE282559_Per0_fatbody_normalizedcounts_2.csv.gz	Csv
	GSE282559_W_fatbody_normalizedcounts_2.csv.gz	Csv

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Project description:Eukaryotic circadian clocks include transcriptional/translational feedback loops that drive 24-hour rhythms of transcription.These transcriptional rhythms underlie oscillations of protein abundance, thereby mediating circadian rhythms of behavior, physiology, and metabolism. Numerous studies over the last decade have employed microarrays to profile circadian transcriptional rhythms in various organisms and tissues. Here we use RNA sequencing (RNA-Seq) to profile the circadian transcriptome of *Drosophila melanogaster* brain from wild-type and *period*-null clock-defective animals. We identify several hundred transcripts whose abundance oscillates with 24-hour periods, including a number of non-coding RNAs (ncRNAs) that were not identified in previous microarray studies. Of particular interest are *U snoRNA host genes* (*Uhgs*), a family of cycling ncRNAs that encode the precursors of over 50 box C/D snoRNAs, key regulators of ribosomal biogenesis. Transcriptional profiling at the level of individual exons reveals alternative splice isoforms for many genes whose relative abundances are regulated by either *period* or circadian time, although the effect of circadian time is muted in comparison to that of *period*. Interestingly, *period* loss-of-function significantly alters the frequency of RNA editing at a number of editing sites, suggesting an unexpected link between a key circadian gene and RNA editing. We also identify tens of thousands of novel splicing events beyond those previously annotated by the modENCODE consortium, including several that affect key circadian genes. These studies demonstrate extensive circadian control of ncRNA expression, reveal the extent of clock control of alternative splicing and RNA editing, and provide a novel, genome-wide map of splicing in *Drosophila* brain. RNA-Seq transcriptional profiling of Drosophila brains from wildtype and period loss-of-function (per0) flies with time points taken over two days in constant darkness. Time points at CT24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, and 68. 10-12 brains per time point.

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

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