Leptin receptor-expressing nucleus tractus solitarius neurons suppress food intake independently of GLP1 in mice
Leptin receptor-expressing nucleus tractus solitarius neurons suppress food intake independently of GLP1 in mice
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DOI：
10.1172/jci.insight.134359
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发表时间：
2020-04-09
期刊：
影响因子：
8
通讯作者：
Myers, Martin G., Jr.
中科院分区：
文献类型：
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作者：
Cheng, Wenwen;Ndoka, Ermelinda;Myers, Martin G., Jr.
孤束核表达瘦素受体（表达 LepRb）的神经元（NTS；LepRb(NTS) 神经元）接收肠道信号，与瘦素作用协同抑制食物摄入。表达前胰高血糖素原 (Ppg)（并产生抑制食物摄入的 PPG 裂解产物胰高血糖素样肽 1 [GLP1]）的 NTS 神经元代表小鼠 LepRb(NTS) 细胞的一个亚群。使用 Lein(cre)、Ppg(cre) 和 Ppg(fl) 小鼠系，以及设计药物专门激活的设计受体 (DREADD)，我们研究了 Ppg 在 GLP1(NTS) 和 LepRP(NTS) 细胞中控制食物摄入和能量平衡的作用。我们发现，在发育早期或成年小鼠中，NTS Ppg(fl) 的 cre 依赖性消融未能改变能量平衡，这表明独立于 NTS GLP1 的途径对于长期控制食物摄入的重要性。一致的是，虽然激活 GLP1(NTS) 细胞会减少食物摄入量，但 LepRb(NTS) 细胞会产生更大、更持久的效果。此外，虽然 NTS Ppg(fl) 的消融削弱了 GLP1(NTS) 神经元在激活过程中抑制食物摄入的能力，但它并不影响 LepRb(NTS) 细胞对食物摄入的抑制。虽然 Ppg/GLP1 介导的神经传递在 GLP1(NTS) 细胞适度的食欲抑制作用中起着核心作用，但 LepRb(NTS) 细胞参与的其他途径在抑制食物摄入方面占主导地位。
Leptin receptor-expressing (LepRb-expressing) neurons of the nucleus tractus solitarius (NTS; LepRb(NTS) neurons) receive gut signals that synergize with leptin action to suppress food intake. NTS neurons that express preproglucagon (Ppg) (and that produce the food intake-suppressing PPG cleavage product glucagon-like peptide-1 [GLP1]) represent a subpopulation of mouse LepRb(NTS) cells. Using Lein(cre), Ppg(cre), and Ppg(fl) mouse lines, along with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we examined roles for Ppg in GLP1(NTS) and LepRP(NTS) cells for the control of food intake and energy balance. We found that the cre-dependent ablation of NTS Ppg(fl) early in development or in adult mice failed to alter energy balance, suggesting the importance of pathways independent of NTS GLP1 for the long-term control of food intake. Consistently, while activating GLP1(NTS) cells decreased food intake, LepRb(NTS) cells elicited larger and more durable effects. Furthermore, while the ablation of NTS Ppg(fl) blunted the ability of GLP1(NTS) neurons to suppress food intake during activation, it did not impact the suppression of food intake by LepRb(NTS) cells. While Ppg/GLP1-mediated neurotransmission plays a central role in the modest appetite-suppressing effects of GLP1(NTS) cells,additional pathways engaged by LepRb(NTS) cells dominate for the suppression of food intake.