The thirsty fly: Ion transport peptide (ITP) is a novel endocrine regulator of water homeostasis in Drosophila

Animals need to continuously adjust their water metabolism to the internal and external conditions. Homeostasis of body fluids thus requires tight regulation of water intake and excretion, and a balance between ingestion of water and solid food. Here, we investigated how these processes are coordinated in Drosophila melanogaster. We identified the first thirst-promoting and anti-diuretic hormone of Drosophila, encoded by the gene Ion transport peptide (ITP). This endocrine regulator belongs to the CHH (crustacean hyperglycemic hormone) family of peptide hormones. Using genetic gain- and loss-of-function experiments, we show that ITP signaling acts analogous to the human vasopressin and renin-angiotensin systems; expression of ITP is elevated by dehydration of the fly, and the peptide increases thirst while repressing excretion, promoting thus conservation of water resources. ITP responds to both osmotic and desiccation stress, and dysregulation of ITP signaling compromises the fly’s ability to cope with these stressors. In addition to the regulation of thirst and excretion, ITP also suppresses food intake. Altogether, our work identifies ITP as an important endocrine regulator of thirst and excretion, which integrates water homeostasis with feeding of Drosophila.

动物需持续调整自身水代谢以适配内外部环境变化。因此，体液稳态需要严格调控水的摄入与排泄，并维持水分摄入与固体食物摄取之间的动态平衡。本研究以黑腹果蝇（Drosophila melanogaster）为模型，探究上述生理过程的协同调控机制。我们首次鉴定出果蝇体内由离子转运肽（Ion transport peptide，ITP）基因编码的促渴抗利尿激素。该内分泌调节因子属于CHH（crustacean hyperglycemic hormone，甲壳类高血糖激素）肽激素家族。通过功能获得与功能丧失遗传实验，我们发现ITP信号通路的作用模式与人类血管加压素及肾素-血管紧张素系统相似；果蝇脱水会上调ITP的表达，该肽类物质可增强渴感并抑制排泄，进而促进水资源的保留。ITP可响应渗透压应激与干燥应激，而ITP信号通路失调会削弱果蝇应对这类应激的能力。除调控渴感与排泄外，ITP还可抑制食物摄入。综上，本研究鉴定ITP为调控渴感与排泄的重要内分泌调节因子，它将果蝇的水稳态与摄食行为整合为统一的生理过程。