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KAIST, 현 Yale University

Science, May 21 2026, 392 (6800) | https://doi.org/10.1126/science.adv3355 Complex interplay of neuronal and hormonal gut-brain responses to essential amino acid deficit

Boram Kim^#1, Seongju Lee^#1, Hyeyeon Bae^1,2, Shinhye Kim², Jong-Hoon Won^1,2, Dongwoo Kim^1,2, Byungkwon Jung², Makoto I Kanai³, Sung-Eun Yoon⁴, Yangkyun Oh^5*, Won-Jae Lee^6*, Greg S B Suh^1,2,4,7*

¹Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
²Institute for Basic Science (IBS), Center for Microbiome-Body-Brain Physiology, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea.
³Department of Cell Biology, NYU Grossman School of Medicine, New York, NY, USA.
⁴Department of Life Sciences, Korea Drosophila Resource Center (KDRC), Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea.
⁵Department of Life Science, College of Natural Sciences, Ewha Womans University, Seoul, Republic of Korea.
⁶National Creative Research Initiative Center for Hologenomics, School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
⁷Department of Integrative Neuroscience & Physiology (INP), Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea.

^#These authors contributed equally to this work.
^*Corresponding authors: Y.O.; W.-J.L.; G.S.B.S.

Abstract

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.

논문소개전체 설명

These findings identify gut-brain signaling systems that respond to protein deficiency and drive EAA-specific appetite. Gut-derived CNMa engages both neuronal and hormonal pathways to activate key neuronal populations that promote EAA intake while suppressing competing nutrients, such as carbohydrates. The observation that EAA-specific appetite is induced during protein deprivation independently of FGF21 in mice suggests the existence of previously unrecognized pathways regulating EAA-specific appetite, opening new directions for understanding the physiological mechanisms that maintain amino acid homeostasis

논문정보

형식Research article
게재일2026년 05월 (BRIC 등록일 2026-05-22)
연구진국내(교신)+국외 연구진
분야 생명과학 > 신경생물학

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