Leptin suppresses development of GLP-1 inputs to the paraventricular nucleus of the hypothalamus.
Leptin suppresses development of GLP-1 inputs to the paraventricular nucleus of the hypothalamus.
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DOI：
10.7554/elife.59857
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发表时间：
2020-11-18
期刊：
影响因子：
7.7
通讯作者：
Simerly R
中科院分区：
文献类型：
--
作者：
Biddinger JE;Lazarenko RM;Scott MM;Simerly R
孤立束核（NTS）对于内脏器官信号的中枢整合至关重要，它含有胰高血糖素前原（PPG）神经元，在小鼠中表达瘦素受体，并向下丘脑室旁核（PVH）发送直接投射。在这里，我们可视化了瘦素缺乏的Lepob/ob小鼠中PPG神经元的投影，发现PPG神经元的投影与对照组相比升高，并且在缺乏功能性神经元瘦素受体的LepRbTB/TB小鼠中，PPG的投影通过靶向拯救瘦素受体而正常化。此外，Lepob/ob和LepRbTB/TB小鼠在迷走神经刺激后显示PVH中的神经元激活水平增加，表达GLP-1受体的PVH神经元的全细胞贴片记录显示兴奋性神经传递增强，这表明瘦素细胞自主地抑制PPG神经元的兴奋性传入，从而减少内脏感觉信息对PVH中表达GLP-1受体的神经元的影响。
The nucleus of the solitary tract (NTS) is critical for the central integration of signals from visceral organs and contains preproglucagon (PPG) neurons, which express leptin receptors in the mouse and send direct projections to the paraventricular nucleus of the hypothalamus (PVH). Here, we visualized projections of PPG neurons in leptin-deficient Lepob/ob mice and found that projections from PPG neurons are elevated compared with controls, and PPG projections were normalized by targeted rescue of leptin receptors in LepRbTB/TB mice, which lack functional neuronal leptin receptors. Moreover, Lepob/ob and LepRbTB/TB mice displayed increased levels of neuronal activation in the PVH following vagal stimulation, and whole-cell patch recordings of GLP-1 receptor-expressing PVH neurons revealed enhanced excitatory neurotransmission, suggesting that leptin acts cell autonomously to suppress representation of excitatory afferents from PPG neurons, thereby diminishing the impact of visceral sensory information on GLP-1 receptor-expressing neurons in the PVH.