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Mechanosensation of the heart and gut elicits hypometabolism and vigilance in mice
Nature Metabolism ( IF 18.9 ) Pub Date : 2025-01-17 , DOI: 10.1038/s42255-024-01205-6
Karen A. Scott, Yalun Tan, Dominique N. Johnson, Khalid Elsaafien, Caitlin Baumer-Harrison, Rebeca Méndez-Hernández, Matthew K. Kirchner, Sophia A. Eikenberry, Jessica M. Sa, Javier E. Stern, Guillaume de Lartigue, Annette D. de Kloet, Eric G. Krause

Interoception broadly refers to awareness of one’s internal milieu. Although the importance of the body-to-brain communication that underlies interoception is implicit, the vagal afferent signalling and corresponding brain circuits that shape perception of the viscera are not entirely clear. Here, we use mice to parse neural circuits subserving interoception of the heart and gut. We determine that vagal sensory neurons expressing the oxytocin receptor (Oxtr), referred to as NGOxtr, send projections to cardiovascular or gastrointestinal tissues and exhibit molecular and structural features indicative of mechanosensation. Chemogenetic excitation of NGOxtr decreases food and water consumption, and remarkably, produces a torpor-like phenotype characterized by reductions in cardiac output, body temperature and energy expenditure. Chemogenetic excitation of NGOxtr also creates patterns of brain activity associated with augmented hypothalamic–pituitary–adrenal axis activity and behavioural indices of vigilance. Recurrent excitation of NGOxtr suppresses food intake and lowers body mass, indicating that mechanosensation of the heart and gut can exert enduring effects on energy balance. These findings suggest that the sensation of vascular stretch and gastrointestinal distention may have profound effects on whole-body metabolism and, possibly, mental health.



中文翻译:


心脏和肠道的机械感觉会引起小鼠的代谢减退和警觉



内感受广义上是指对一个人内部环境的意识。尽管作为内感受基础的体脑通信的重要性是隐含的,但塑造内脏感知的迷走神经传入信号和相应的大脑回路尚不完全清楚。在这里,我们使用小鼠来解析服务于心脏和肠道内感受的神经回路。我们确定表达催产素受体 (Oxtr),称为 NGOxtr)的迷走神经感觉神经元向心血管或胃肠道组织发送投射,并表现出指示机械感觉的分子和结构特征。NGOxtr 的化学遗传学兴奋减少了食物和水的消耗,并显着产生了一种以心输出量、体温和能量消耗减少为特征的 torpor 样表型。NGOxtr 的化学遗传学兴奋还会产生与下丘脑-垂体-肾上腺轴活动增强和警觉行为指数相关的大脑活动模式。NGOxtr 的反复兴奋会抑制食物摄入并降低体重,表明心脏和肠道的机械感觉可以对能量平衡产生持久的影响。这些发现表明,血管拉伸感和胃肠道扩张感可能对全身新陈代谢产生深远影响,甚至可能对心理健康产生深远影响。

更新日期:2025-01-17
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