Department of Physiology, Medical College of Georgia at Augusta University , Augusta, Georgia.
Am J Physiol Endocrinol Metab. 2019 May 1;316(5):E719-E728. doi: 10.1152/ajpendo.00562.2018. Epub 2019 Feb 5.
Previous studies suggest that weight loss occurs when leptin receptors in both the forebrain and hindbrain are activated. Experiments described here tested whether this integration is mediated through a neural connection or by leptin diffusion through the subarachanoid space. If the hypothalamus and hindbrain communicated through a neural pathway, then a very low dose of leptin infused directly into the nucleus of the solitary tract (NTS) would enhance the response to third ventricle (3V) leptin but would have no effect if infused into the fourth ventricle (4V). A 12-day infusion of 10 ng/24 h into the 4V or the NTS reduced body fat. Leptin at 5 ng/24 h into the 4V or NTS had no effect on food intake or body composition, but infusion of 5 ng of leptin/24 h into the NTS combined with a 3V injection of 0.1 μg of leptin inhibited food intake between 6 and 12 h after injection. Cumulative intake was inhibited for up to 36 h. 3V leptin had no effect on food intake of rats receiving the 4V leptin infusion. Similar results were found using infusions of 5 ng leptin/24 h and a 3V injection of 0.025 μg leptin. These data suggest that activation of leptin receptors in the NTS lowers the threshold for response to leptin in the forebrain through a neural network.
先前的研究表明，当下脑神经和后脑的瘦素受体被激活时，就会发生体重减轻。这里描述的实验测试了这种整合是否是通过神经连接或通过瘦素在蛛网膜下腔扩散来介导的。如果下丘脑和后脑通过神经通路进行交流，那么直接注入孤束核（NTS）的极低剂量瘦素将增强对第三脑室（3V）瘦素的反应，但如果注入第四脑室（4V）则没有效果。连续 12 天以 10ng/24h 的剂量注入 4V 或 NTS 会减少体脂。以 5ng/24h 的剂量注入 4V 或 NTS 的瘦素对食物摄入或身体成分没有影响，但以 5ng 的瘦素/24h 注入 NTS 并结合 3V 注射 0.1μg 的瘦素会抑制注射后 6 至 12 小时的食物摄入。累积摄入量抑制长达 36 小时。接受 4V 瘦素输注的大鼠的 3V 瘦素对食物摄入没有影响。使用 5ng 瘦素/24h 输注和 3V 注射 0.025μg 瘦素也得到了类似的结果。这些数据表明，NTS 中瘦素受体的激活通过神经网络降低了对前脑瘦素反应的阈值。
