小柯机器人

德国环境卫生研究中心Cristina García-Cáceres、Matthias H. Tschöp等研究人员合作发现，肥胖相关的高瘦素血症会改变下丘脑的胶质血管界面来促进高血压。2021年5月4日，《细胞—代谢》杂志在线发表了这项研究成果。

研究人员发现，肥胖与血清瘦素的增加触发了在调节血液动态动态平衡的自主神经中枢中微血管结构的选择性扩展。通过使用一系列的细胞和区域特定的功能丧失和获得功能模型，研究人员表明这种病理生理过程取决于瘦素下游的下丘脑星形胶质细胞缺氧诱导因子1α-血管内皮生长因子（HIF1α-VEGF）信号。

重要的是，星形胶质细胞中HIF1α-VEGF途径破坏的几种不同模型不仅受到肥胖引起的下丘脑血管病保护，而且还受到交感神经亢进或动脉高血压的保护。这些结果表明，高瘦素血症通过下丘脑星形胶质细胞中的HIF1α-VEGF信号级联反应促进肥胖诱导的高血压，同时建立了连接下丘脑微血管结构与控制全身血压的新型机制联系。

据介绍，微血管和大血管系统的病理是新陈代谢综合症的标志，它可以导致血压长期升高。但是，仍需弄清涉及的潜在病理机制。

附：英文原文

Title: Obesity-associated hyperleptinemia alters the gliovascular interface of the hypothalamus to promote hypertension

Author: Tim Gruber, Chenchen Pan, Raian E. Contreras, Tobias Wiedemann, Donald A. Morgan, Alicja A. Skowronski, Sandrine Lefort, Cahuê De Bernardis Murat, Ophelia Le Thuc, Beata Legutko, Francisco J. Ruiz-Ojeda, María de la Fuente-Fernández, Angel Luis García-Villalón, Daniel González-Hedstrm, Melanie Huber, Klara Szigeti-Buck, Timo D. Müller, Siegfried Ussar, Paul Pfluger, Steve C. Woods, Ali Ertürk, Charles A. LeDuc, Kamal Rahmouni, Miriam Granado, Tamas L. Horvath, Matthias H. Tschp, Cristina García-Cáceres

Issue&Volume: 2021-05-04

Abstract: Pathologies of the micro- and macrovascular systems are a hallmark of the metabolic syndrome, which can lead to chronically elevated blood pressure. However, the underlying pathomechanisms involved still need to be clarified. Here, we report that an obesity-associated increase in serum leptin triggers the select expansion of the micro-angioarchitecture in pre-autonomic brain centers that regulate hemodynamic homeostasis. By using a series of cell- and region-specific loss- and gain-of-function models, we show that this pathophysiological process depends on hypothalamic astroglial hypoxia-inducible factor 1α-vascular endothelial growth factor (HIF1α-VEGF) signaling downstream of leptin signaling. Importantly, several distinct models of HIF1α-VEGF pathway disruption in astrocytes are protected not only from obesity-induced hypothalamic angiopathy but also from sympathetic hyperactivity or arterial hypertension. These results suggest that hyperleptinemia promotes obesity-induced hypertension via a HIF1α-VEGF signaling cascade in hypothalamic astrocytes while establishing a novel mechanistic link that connects hypothalamic micro-angioarchitecture with control over systemic blood pressure.

DOI: 10.1016/j.cmet.2021.04.007

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00173-X

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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