小柯机器人

法国里尔大学Vincent Prevot、Caroline Bonner等研究人员合作发现，伸长细胞调控下丘脑的利拉鲁肽摄入及其减肥作用。这一研究成果于2022年6月17日在线发表在国际学术期刊《细胞—代谢》上。

研究人员证明利拉鲁肽通过被称为伸长细胞的专门上皮细胞穿梭到小鼠下丘脑的目标细胞，从而绕过血脑屏障。选择性地沉默伸长细胞中的胰高血糖素样肽一受体（GLP1R）或通过肉毒杆菌神经毒素的表达来抑制伸长细胞的转运，不仅阻碍了利拉鲁肽进入大脑的运输及其对目标下丘脑神经元的激活，而且还阻止了其对食物摄入、体重和脂肪量以及脂肪酸氧化的抗肥胖效应。

总之，这些惊人的数据表明，利拉鲁肽诱导的下丘脑神经元激活及其下游的代谢效应是由其转运到下丘脑中轴的伸长细胞所促成的，这些发现加强了伸长细胞作为代谢平衡的关键调节器的概念。

据了解，利拉鲁肽是一种抗糖尿病药物和GLP1R的激动剂，最近被批准用于治疗患有或不患有2型糖尿病个体的肥胖症。尽管它具有广泛的代谢益处，但利拉鲁肽的作用机制和部位仍然不清楚。

附：英文原文

Title: Tanycytes control hypothalamic liraglutide uptake and its anti-obesity actions

Author: Monica Imbernon, Chiara Saponaro, Hans Christian Cederberg Helms, Manon Duquenne, Daniela Fernandois, Eleonora Deligia, Raphael G.P. Denis, Daniela Herrera Moro Chao, Sowmyalakshmi Rasika, Bart Staels, Franois Pattou, Frank W. Pfrieger, Birger Brodin, Serge Luquet, Caroline Bonner, Vincent Prevot

Issue&Volume: 2022-06-17

Abstract: Liraglutide, an anti-diabetic drug and agonist of the glucagon-like peptide one receptor(GLP1R), has recently been approved to treat obesity in individuals with or withouttype 2 diabetes. Despite its extensive metabolic benefits, the mechanism and siteof action of liraglutide remain unclear. Here, we demonstrate that liraglutide isshuttled to target cells in the mouse hypothalamus by specialized ependymoglial cellscalled tanycytes, bypassing the blood-brain barrier. Selectively silencing GLP1R intanycytes or inhibiting tanycytic transcytosis by botulinum neurotoxin expressionnot only hampers liraglutide transport into the brain and its activation of targethypothalamic neurons, but also blocks its anti-obesity effects on food intake, bodyweight and fat mass, and fatty acid oxidation. Collectively, these striking data indicatethat the liraglutide-induced activation of hypothalamic neurons and its downstreammetabolic effects are mediated by its tanycytic transport into the mediobasal hypothalamus,strengthening the notion of tanycytes as key regulators of metabolic homeostasis.

DOI: 10.1016/j.cmet.2022.06.002

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00222-4

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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