Leptin and the control of food intake: Neurons in the nucleus of the solitary tract are activated by both gastric distension and leptin
Leptin and the control of food intake: Neurons in the nucleus of the solitary tract are activated by both gastric distension and leptin
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DOI：
10.1210/en.2006-1572
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发表时间：
2007-05-01
期刊：
影响因子：
4.8
通讯作者：
Grill, Harvey J.
中科院分区：
文献类型：
--
作者：
Huo, Lihong;Maeng, Lisa;Grill, Harvey J.
瘦素通过一种未知的机制减少食物摄入。研究表明，前脑脑室瘦素的传递增加了胃肠道刺激对摄入的抑制作用，并增强了孤束核内侧亚核神经元对胃扩张的电生理反应。然而，前脑脑室递送没有明确的神经解剖部位介导瘦素对摄入的影响。通过磷酸化信号传感器和转录激活因子3免疫组织化学对大鼠和小鼠的详细解剖分析表明，后脑瘦素反应神经元仅位于mNTS内。在这里，我们研究1)瘦素和胃胀是否影响相同的mNTS神经元，2)胃胀的摄入抑制作用是否通过后脑瘦素的传递而增强。胃球囊扩张或假扩张25分钟后，给大鼠注射瘦素或载药，35分钟后处死。磷酸化信号转导因子和转录激活因子3和c-Fos的双荧光免疫组化显示，约40%的瘦素反应细胞也对胃胀有反应。然后开发了一个范例来检查瘦素和胃膨胀量对摄入抑制的关系。在阈下水平，后脑室瘦素或扩张容量没有影响。当两者结合时，会产生一种相互作用，显著减少食物摄入量。我们得出结论：1)后脑的瘦素反应神经元主要位于后脑区水平的mNTS，这是GI系统的一个关键迷走神经传入投射区；2)胃胀激活了mNTS中显著比例的瘦素反应神经元；3)输送到后脑的瘦素足以增强胃胀量的摄入抑制作用，否则胃胀量是无效的。这些结果与瘦素通过与GI信号处理的相互作用直接作用于mNTS内的神经元以减少食物摄入的假设相一致。
Leptin reduces food intake by an unspecified mechanism. Studies show that forebrain ventricular leptin delivery increases the inhibitory effects of gastrointestinal (GI) stimulation on intake and amplifies the electrophysiological response to gastric distension in neurons of the medial subnucleus of the nucleus tractus solitarius (mNTS). However, forebrain ventricular delivery leaves unspecified the neuroanatomical site(s) mediating leptin's effect on intake. Detailed anatomical analysis in rats and mice by phosphorylated signal transducer and activator of transcription 3 immunohistochemistry shows that hindbrain leptin-responsive neurons are located exclusively within the mNTS. Here, we investigate 1) whether leptin and gastric distension affect the same mNTS neurons and 2) whether the intake-inhibitory action of gastric distension is potentiated by hindbrain leptin delivery. Twenty-five minutes after gastric balloon distension or sham distension, rats were injected with leptin or vehicle and killed 35 min later. Double-fluorescent immunohistochemistry for phosphorylated signal transducer and activator of transcription 3 and c-Fos revealed that about 40% of leptin-responsive cells also respond to gastric distension. A paradigm was then developed to examine the relationship between leptin and gastric distension volume on intake inhibition. At subthreshold levels, hindbrain ventricular leptin or distension volume were without effect. When combined, an interaction occurred that significantly reduced food intake. We conclude that 1) leptin-responsive neurons in the hindbrain are primarily located in the mNTS at the level of the area postrema, a key vagal afferent projection zone of the GI system; 2) a significant proportion of leptin-responsive neurons in the mNTS are activated by stomach distension; and 3) leptin delivered to the hindbrain is sufficient to potentiate the intake-suppressive effects of an otherwise ineffective volume of gastric distension. These results are consistent with the hypothesis that leptin acts directly on neurons within the mNTS to reduce food intake through an interaction with GI signal processing.