Short neuropeptide F regulates the starvation mediated enhanced locomotor activity in Drosophila

The circadian clock regulates various behavioral, metabolic and physiological processes to occur at the most suitable time of the day. Internal energy stores and nutrient availability modulates the most apparent circadian clock mediated locmotor activity rhythm in Drosophila. Although previous studies unraveled the role of circadian clock in metabolism and activity rest rhythm, the precise pathway through which the circadian neuropeptidergic signaling regulates internal energy storage and the starvation-mediated increase in activity resembling foraging remains largely unclear. This study was aimed to elucidate the role of circadian neuropeptide, short neuropeptide F (sNPF) in triglyceride metabolism, starvation resistance and starvation-mediated increased locomotor activity in Drosophila. The results showed that snpf transcripts exhibits significant rhythmicity in wild type flies under 12:12 hour light-dark cycles (LD) and constant darkness (DD) whereas snpf transcript level in period null flies did not exhibit any significant rhythmicity under LD. Knockdown of sNPF in circadian clock neurons reduced the triglyceride level, starvation resistance and increased the starvation-mediated hyperactivity response after 24 hour of starvation. Further studies showed that knock down of sNPF receptors (sNPFR) expressed in insulin producing cells (IPC) increased the starvation resistance and reduced starvation-induced hyperactivity response after 24 hour of starvation. Collectively, our results suggest that transcriptional oscillation of snpf mRNA is endogenously controlled by the circadian clock and elucidate the role of sNPF in modulating locomotor activity in accordance with the nutrient availability in Drosophila.

生物钟（circadian clock）可调控各类行为、代谢与生理过程，使其于一日中最适宜的时段发生。体内能量储备与养分可获得性，会调控果蝇（Drosophila）中最显著的、由生物钟介导的运动活动节律。尽管既往研究已阐明生物钟在代谢与活动-休息节律中的作用，但由神经肽能信号通路介导的生物钟，调控体内能量储备以及饥饿诱导的类觅食运动增强的确切通路，目前仍尚未完全明晰。本研究旨在阐明生物钟神经肽——短神经肽F（short neuropeptide F, sNPF）在果蝇甘油三酯代谢、饥饿抗性以及饥饿诱导的运动活动增强中的作用。研究结果显示，在12小时光照:12小时黑暗的光暗循环（light-dark cycles, LD）与持续黑暗（constant darkness, DD）条件下，野生型果蝇的snpf转录本呈现显著节律性；而在周期基因（period）缺失突变体果蝇中，LD条件下的snpf转录本水平未表现出任何显著节律性。在生物钟神经元中敲低sNPF，会降低甘油三酯水平与饥饿抗性，并在饥饿24小时后增强饥饿诱导的过度活动反应。进一步研究显示，在胰岛素分泌细胞（insulin producing cells, IPC）中敲低sNPF受体（sNPFR），会提升饥饿抗性，并在饥饿24小时后降低饥饿诱导的过度活动反应。综上，本研究结果表明，snpf mRNA的转录振荡由生物钟内源调控，并阐明了sNPF在果蝇中依据养分可获得性调控运动活动的作用。