Hedonic eating is controlled by dopamine neurons that oppose GLP-1R satiety

• 成果类型: Article
• 署名作者: Zhu, Zhenggang; Gong, Rong; Rodriguez, Vicente; Quach, Kathleen T.; Chen, Xinyu; Sternson, Scott M.
• 署名单位: University of California System; University of California San Diego; Howard Hughes Medical Institute; Howard Hughes Medical Institute; University of California System; University of California San Diego; Beijing Normal University; Chinese Institute for Brain Research, Beijing
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10122
• DOI: 10.1126/science.adt0773
• 发表日期: 2025-03-28
• 关键词: lateral hypothalamus; gustatory stimuli; licking behavior; gaba neurons; reward; food; palatability; prediction; circuits; microstructure

摘要

Hedonic eating is defined as food consumption driven by palatability without physiological need. However, neural control of palatable food intake is poorly understood. We discovered that hedonic eating is controlled by a neural pathway from the peri-locus ceruleus to the ventral tegmental area (VTA). Using photometry-calibrated optogenetics, we found that VTA dopamine (VTADA) neurons encode palatability to bidirectionally regulate hedonic food consumption. VTADA neuron responsiveness was suppressed during food consumption by semaglutide, a glucagon-like peptide receptor 1 (GLP-1R) agonist used as an antiobesity drug. Mice recovered palatable food appetite and VTADA neuron activity during repeated semaglutide treatment, which was reversed by consumption-triggered VTADA neuron inhibition. Thus, hedonic food intake activates VTADA neurons, which sustain further consumption, a mechanism that opposes appetite reduction by semaglutide.