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<p>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 <i>Drosophila</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月14日

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  • Nadja Ahrentløv,
  • Olga Kubrak,
  • Mette Lassen,
  • Alina Malita,
  • Takashi Koyama,
  • Amalie S. Frederiksen,
  • Casper M. Sigvardsen,
  • Alphy John,
  • Pernille E. H. Madsen,
  • Kenneth V. Halberg,
  • Stanislav Nagy,
  • Cordelia Imig,
  • Erik A. Richter,
  • Michael J. Texada,
  • Kim Rewitz

摘要

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.