{"title":"Identification of a neural basis for energy expenditure in the mouse arcuate hypothalamus.","authors":"Ting Wang, Shuping Han, Yaxin Wang, Yaning Li, Yuxiao Li, Zhifang Xing, Shuangfeng Zhang, Yu Xia, Feipeng Zhu, Zhen-Hua Chen, Yu Zheng Li, Jingjing Wang, Mingrui Xu, Qinghua Liu, Man Jiang, Xiaohong Xu, Xiangning Li, Hui Gong, Peng Cao, Qing-Feng Wu","doi":"10.1016/j.neuron.2025.08.021","DOIUrl":null,"url":null,"abstract":"<p><p>Given the evolutionary instinct for caloric intake and frequent weight rebound after diet or drug cessation, increasing energy expenditure emerges as an alternative obesity treatment. Environmental cues such as cold and seasonal light prompt the brain to adjust energy expenditure, yet the coordinating neural mechanisms remain poorly understood. Here, we identify a hypothalamic GABAergic neuronal subtype, marked by Crabp1, that targets multiple nuclei to regulate energy expenditure in mice. Silencing Crabp1 neurons reduces physical activity, body temperature, and adaptive thermogenesis, leading to obesity, whereas activation increases energy expenditure and mitigates diet-induced obesity. Structural and functional analyses reveal that Crabp1 neurons promote energy metabolism through a \"one-to-many\" projection pattern. While Crabp1 neurons are activated by cold exposure and physical activity, prolonged light exposure abrogates their firing, which mediates light-induced metabolic disorder. Together, we reveal a neural basis that integrates various physiological and environmental stimuli to control energy expenditure and body weight.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0000,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuron","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.neuron.2025.08.021","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Given the evolutionary instinct for caloric intake and frequent weight rebound after diet or drug cessation, increasing energy expenditure emerges as an alternative obesity treatment. Environmental cues such as cold and seasonal light prompt the brain to adjust energy expenditure, yet the coordinating neural mechanisms remain poorly understood. Here, we identify a hypothalamic GABAergic neuronal subtype, marked by Crabp1, that targets multiple nuclei to regulate energy expenditure in mice. Silencing Crabp1 neurons reduces physical activity, body temperature, and adaptive thermogenesis, leading to obesity, whereas activation increases energy expenditure and mitigates diet-induced obesity. Structural and functional analyses reveal that Crabp1 neurons promote energy metabolism through a "one-to-many" projection pattern. While Crabp1 neurons are activated by cold exposure and physical activity, prolonged light exposure abrogates their firing, which mediates light-induced metabolic disorder. Together, we reveal a neural basis that integrates various physiological and environmental stimuli to control energy expenditure and body weight.
期刊介绍:
Established as a highly influential journal in neuroscience, Neuron is widely relied upon in the field. The editors adopt interdisciplinary strategies, integrating biophysical, cellular, developmental, and molecular approaches alongside a systems approach to sensory, motor, and higher-order cognitive functions. Serving as a premier intellectual forum, Neuron holds a prominent position in the entire neuroscience community.