Gut-brain communication by distinct sensory neurons differently controls feeding and glucose metabolism.
Gut-brain communication by distinct sensory neurons differently controls feeding and glucose metabolism.
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DOI：
10.1016/j.cmet.2021.05.002
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发表时间：
2021-07-06
期刊：
影响因子：
29
通讯作者：
Fenselau H
中科院分区：
文献类型：
--
作者：
Borgmann D;Ciglieri E;Biglari N;Brandt C;Cremer AL;Backes H;Tittgemeyer M;Wunderlich FT;Brüning JC;Fenselau H
感觉神经元将肠道来源的信号传递到大脑，但不同群体的分子和功能组织仍不清楚。在这里，我们采用交叉遗传操作来探测不同感觉神经元的摄食和糖调节功能。我们重建了许多分子定义的迷走神经和脊髓传入神经的肠道神经支配模式，并确定其下游的大脑目标。双向化学发生操纵，加上行为和电路映射分析，表明肠神经支配，胰高血糖素样肽1受体（GLP 1 R）表达迷走神经传入中继arrhoxigenic信号臂旁核神经元，控制进餐终止。此外，GLP 1 R迷走神经传入激活改善葡萄糖耐量，并且其抑制独立于食物摄入升高血糖水平。相反，肠神经支配，GPR 65表达迷走神经传入刺激增加肝葡萄糖的生产和激活臂旁神经元，控制normoblasts，但他们是不稳定的进食调节。因此，不同的肠道神经支配的感觉神经元差异控制喂养和葡萄糖调节神经回路，并可能提供特定的目标代谢控制。感觉神经元的交叉映射识别不同的肠道神经支配模式肠道神经支配GLP 1 R+迷走神经传入将促神经信号传递给脑干神经元肠道神经支配GPR 65+迷走神经传入刺激增加肝脏葡萄糖产生GLP 1 R+迷走神经传入活动是控制进食期间的食欲所必需的Borgmann et al.设计一种交叉遗传学方法来探测分子定义的感觉神经元在肠-脑通讯中的作用。他们发现，不同的肠道支配迷走神经传入差异控制食物摄入和外周葡萄糖代谢，并在大脑中参与不同的下游回路。
Sensory neurons relay gut-derived signals to the brain, yet the molecular and functional organization of distinct populations remains unclear. Here, we employed intersectional genetic manipulations to probe the feeding and glucoregulatory function of distinct sensory neurons. We reconstruct the gut innervation patterns of numerous molecularly defined vagal and spinal afferents and identify their downstream brain targets. Bidirectional chemogenetic manipulations, coupled with behavioral and circuit mapping analysis, demonstrated that gut-innervating, glucagon-like peptide 1 receptor (GLP1R)-expressing vagal afferents relay anorexigenic signals to parabrachial nucleus neurons that control meal termination. Moreover, GLP1R vagal afferent activation improves glucose tolerance, and their inhibition elevates blood glucose levels independent of food intake. In contrast, gut-innervating, GPR65-expressing vagal afferent stimulation increases hepatic glucose production and activates parabrachial neurons that control normoglycemia, but they are dispensable for feeding regulation. Thus, distinct gut-innervating sensory neurons differentially control feeding and glucoregulatory neurocircuits and may provide specific targets for metabolic control. Intersectional mapping of sensory neurons identifies distinct gut innervation patterns Gut-innervating GLP1R+ vagal afferents relay anorexigenic signals to brainstem neurons Gut-innervating GPR65+ vagal afferent stimulation increases hepatic glucose production GLP1R+ vagal afferent activity is required to control glycemia during feeding Borgmann et al. devise an intersectional genetic approach to probe the contribution of molecularly defined sensory neurons in gut-brain communication. They identify that distinct gut-innervating vagal afferents differentially control food intake and peripheral glucose metabolism, and engage distinct downstream circuits in the brain.
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DOI：
10.1523/jneurosci.6451-10.2011
发表时间：
2011-03-30
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cavanaugh DJ;Chesler AT;Jackson AC;Sigal YM;Yamanaka H;Grant R;O'Donnell D;Nicoll RA;Shah NM;Julius D;Basbaum AI
通讯作者：
Basbaum AI
影响因子：
2.9
作者：
Berthoud, HR;Patterson, LM;Neuhuber, WL
通讯作者：
Neuhuber, WL
影响因子：
29
作者：
Campos CA;Bowen AJ;Schwartz MW;Palmiter RD
通讯作者：
Palmiter RD
影响因子：
64.5
作者：
Chang RB;Strochlic DE;Williams EK;Umans BD;Liberles SD
通讯作者：
Liberles SD
影响因子：
64.8
作者：
通讯作者：
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