Complex interplay of neuronal and hormonal gut-brain responses to essential amino acid deficit

• 成果类型: Article
• 署名作者: Kim, Boram; Lee, Seongju; Bae, Hyeyeon; Kim, Shinhye; Won, Jong-Hoon; Kim, Dongwoo; Jung, Byungkwon; Kanai, Makoto I.; Yoon, Sung-Eun; Oh, Yangkyun; Lee, Won-Jae; Suh, Greg S. B.
• 署名单位: Korea Advanced Institute of Science & Technology (KAIST); Institute for Basic Science - Korea (IBS); Gwangju Institute of Science & Technology (GIST); New York University; Gwangju Institute of Science & Technology (GIST); Ewha Womans University; Seoul National University (SNU); Gwangju Institute of Science & Technology (GIST); Osaka Metropolitan University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adv3355
• 发表日期: 2026-05-21
• 页码: eadv3355
• 关键词: food; homeostasis; circuit; hunger; gene; CNMA

摘要

A deficit in dietary protein elicits a nutrient-specific appetite, yet the underlying mechanisms remain poorly understood. In this work, we identify coordinated neuronal and systemic mechanisms in Drosophila that drive an essential amino acid (EAA)-specific appetite. EAA deprivation increases neuropeptide CNMamide (CNMa) expression in gut enterocytes, activating enteric neurons and ellipsoid body neurons in the brain to promote EAA intake through two complementary pathways: a rapid neuronal gut-brain axis and a slower hormonal route. CNMa suppresses the activity of sugar-sensing diuretic hormone 44 (DH44) neurons, thereby reducing carbohydrate intake and biasing feeding toward EAAs. Similarly, protein deprivation in mice promotes an EAA-specific appetite independently of fibroblast growth factor 21 (FGF21). Together, these findings reveal multilayered gut-brain mechanisms that regulate nutrient-specific feeding and maintain EAA homeostasis across species.