Protein-responsive gut hormone tachykinin directs food choice and impacts lifespan

作者：Nadja Ahrentløv, Olga Kubrak, Mette Lassen, Alina Malita, Takashi Koyama, Amalie S Frederiksen, Casper M. Sigvardsen, Alphy John, P. S. Myschetzky S. M. Madsen, Kenneth A. Halberg, Stanislav Nagy, Cordelia Imig, Erik A. Richter, Michael J. Texada, Kim Rewitz · 发表于：Nature Metabolism · 年份：2025 · DOI：10.1038/s42255-025-01267-0 · 被引用次数：29 · 研究领域：Biochemical effects in animals、Diet and metabolism studies、Neuropeptides and Animal Physiology

Animals select food based on hungers that reflect dynamic macronutrient needs, but the hormonal mechanisms underlying nutrient-specific appetite regulation remain poorly defined. Here, we identify tachykinin (Tk) as a protein-responsive gut hormone in Drosophila and female mice, regulated by conserved environmental and nutrient-sensing mechanisms. Protein intake activates Tk-expressing enteroendocrine cells (EECs), driving the release of gut Tk through mechanisms involving target of rapamycin (TOR) and transient receptor potential A1 (TrpA1). In flies, we delineate a pathway by which gut Tk controls selective appetite and sleep after protein ingestion, mediated by glucagon-like adipokinetic hormone (AKH) signalling to neurons and adipose tissue. This mechanism suppresses protein appetite, promotes sugar hunger and modulates wakefulness to align behaviour with nutritional needs. Inhibiting protein-responsive gut Tk prolongs lifespan through AKH, revealing a role for nutrient-dependent gut hormone signalling in longevity. Our results provide a framework for understanding EEC-derived nutrient-specific satiety signals and the role of gut hormones in regulating food choice, sleep and lifespan.