小柯机器人

加拿大麦吉尔大学Maia V. Kokoeva课题组揭示，表达瘦素受体 (LepR)的周细胞介导下丘脑反馈中心访问循环瘦素的通路。这一研究成果于2021年6月14日发表在国际顶尖学术期刊《细胞-代谢》杂志上。

采用活体显微镜检查，他们发现 中基底下丘脑 (MBH)中几乎一半的血管包裹周细胞表达 LepR。周细胞 LepR 的选择性破坏导致食物摄入量增加、脂肪量增加以及附近 LepR 神经元中瘦素依赖性信号的丢失。当静脉注射时，荧光标记的瘦素在下丘脑 LepR 周细胞处积累，在周细胞特异性 LepR 丢失时减弱。因为细胞旁示踪剂也优先保留在 LepR 周细胞，他们在药理学上靶向内皮间连接紧密的调节子，发现它们影响 LepR 神经元信号传导和食物摄入。MBH切片中的光学成像显示，LepR 周细胞对瘦素作出反应，导致持久的强直性钙增加，表明周细胞收缩和血管收缩。

总之，他们的数据表明 LepR 周细胞促进局部的、细胞旁血脑屏障泄漏，使 MBH LepR 神经元能够访问循环瘦素通路。

据了解，关于MBH的LepR神经元如何进入循环瘦素的认知仍处于初级阶段。

附：英文原文

Title: Leptin receptor-expressing pericytes mediate access of hypothalamic feeding centers to circulating leptin

Author: Liliia I. Butiaeva, Tal Slutzki, Hannah E. Swick, Clément Bourguignon, Sarah C. Robins, Xiaohong Liu, Kai-Florian Storch, Maia V. Kokoeva

Issue&Volume: 2021-06-14

Abstract: Knowledge of how leptin receptor (LepR) neurons of the mediobasal hypothalamus (MBH)access circulating leptin is still rudimentary. Employing intravital microscopy, wefound that almost half of the blood-vessel-enwrapping pericytes in the MBH expressLepR. Selective disruption of pericytic LepR led to increased food intake, increasedfat mass, and loss of leptin-dependent signaling in nearby LepR neurons. When deliveredintravenously, fluorescently tagged leptin accumulated at hypothalamic LepR pericytes,which was attenuated upon pericyte-specific LepR loss. Because a paracellular tracerwas also preferentially retained at LepR pericytes, we pharmacologically targetedregulators of inter-endothelial junction tightness and found that they affect LepRneuronal signaling and food intake. Optical imaging in MBH slices revealed a long-lasting,tonic calcium increase in LepR pericytes in response to leptin, suggesting pericyticcontraction and vessel constriction. Together, our data indicate that LepR pericytesfacilitate localized, paracellular blood-brain barrier leaks, enabling MBH LepR neuronsto access circulating leptin.

DOI: 10.1016/j.cmet.2021.05.017

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
官方网址：https://www.cell.com/cell-metabolism/home
投稿链接：https://www.editorialmanager.com/cell-metabolism/default.aspx