Bhatnagar Apoorva, Banerjee Srishti, Das Sandip, Saha Saibal, Murray Greg, Ray Sandipan
Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, India.
Centre for Mental Health and Brain Sciences, Swinburne University of Technology, Melbourne, Australia.
OMICS. 2025 Jul;29(7):320-329. doi: 10.1089/omi.2025.0058. Epub 2025 Jun 25.
Circadian rhythm and the sleep/wake cycle can influence metabolic regulation, eating habits, hormone release, and common chronic health conditions such as obesity, depression, diabetes, and sleep disorders. the fruit fly, with its conserved molecular clocks and accessible assays, has been used as an ideal model system to study biological processes, for example, circadian rhythms, sleep, neurodevelopment, genetics, and behavior. Using an integrated approach combining high-throughput locomotor activity monitoring and untargeted metabolomics, we analyzed the behavioral and metabolic effects of a chronobiotic melatonin. The behavioral activity of fruit flies was recorded using an infrared-based monitoring device, followed by data analysis with open-source data packages ShinyR-DAM and VANESSA. We found that 1 mM and 4 mM melatonin doses significantly increased locomotor activity. Melatonin at a high concentration (4 mM) exhibited a protective effect to reduce mortality in . Despite these changes, melatonin preserved the flies' endogenous bimodal activity pattern, maintaining circadian alignment. Metabolomics analysis using high-performance liquid chromatography-mass spectrometry identified differentially abundant metabolites after melatonin administration compared with the vehicle treatment. We discovered 20 biologically relevant metabolites altered by melatonin, including key perturbations in arginine biosynthesis, alanine/aspartate/glutamate metabolism, and pyrimidine pathways. Notably, melatonin upregulated glutamine, a potential indicator of enhanced neurotransmitter synthesis and broadly modulated amino acid and nucleotide metabolism, suggesting dual roles in neuroprotection and energy homeostasis. This high-throughput omics study uncovers melatonin-induced behavioral and metabolic perturbations in as a model organism, revealing how melatonin modulates locomotor activity and circadian integrity through specific alterations in metabolism.
昼夜节律和睡眠/觉醒周期会影响代谢调节、饮食习惯、激素释放以及肥胖、抑郁、糖尿病和睡眠障碍等常见慢性健康状况。果蝇具有保守的分子时钟且检测方法易于操作，已被用作研究生物过程的理想模型系统，例如昼夜节律、睡眠、神经发育、遗传学和行为。我们采用高通量运动活动监测与非靶向代谢组学相结合的综合方法，分析了生物钟调节因子褪黑素的行为和代谢效应。使用基于红外的监测设备记录果蝇的行为活动，随后用开源数据包ShinyR-DAM和VANESSA进行数据分析。我们发现1 mM和4 mM的褪黑素剂量显著增加了运动活动。高浓度（4 mM）的褪黑素表现出保护作用，可降低果蝇的死亡率。尽管有这些变化，褪黑素仍保留了果蝇内源性双峰活动模式，维持昼夜节律同步。使用高效液相色谱-质谱联用的代谢组学分析确定了褪黑素给药后与载体处理相比差异丰富的代谢物。我们发现20种与生物相关的代谢物被褪黑素改变，包括精氨酸生物合成、丙氨酸/天冬氨酸/谷氨酸代谢和嘧啶途径中的关键扰动。值得注意的是，褪黑素上调了谷氨酰胺，这是神经递质合成增强的潜在指标，并广泛调节氨基酸和核苷酸代谢，表明其在神经保护和能量稳态中具有双重作用。这项高通量组学研究揭示了褪黑素在果蝇这一模式生物中引起的行为和代谢扰动，揭示了褪黑素如何通过代谢的特定改变来调节运动活动和昼夜节律完整性。
