瘦素
小鼠苗条素受体
内科学
内分泌学
周细胞
并行传输
下丘脑
脂肪因子
生物
肥胖
医学
受体
内皮干细胞
体外
生物化学
磁导率
遗传学
膜
作者
Liliia I. Butiaeva,Tal Slutzki,Hannah E. Swick,Clément Bourguignon,Sarah C. Robins,Xiaohong Liu,Kai-Florian Storch,Maia V. Kokoeva
出处
期刊:Cell Metabolism
[Elsevier]
日期:2021-06-14
卷期号:33 (7): 1433-1448.e5
被引量:45
标识
DOI:10.1016/j.cmet.2021.05.017
摘要
Knowledge of how leptin receptor (LepR) neurons of the mediobasal hypothalamus (MBH) access circulating leptin is still rudimentary. Employing intravital microscopy, we found that almost half of the blood-vessel-enwrapping pericytes in the MBH express LepR. Selective disruption of pericytic LepR led to increased food intake, increased fat mass, and loss of leptin-dependent signaling in nearby LepR neurons. When delivered intravenously, fluorescently tagged leptin accumulated at hypothalamic LepR pericytes, which was attenuated upon pericyte-specific LepR loss. Because a paracellular tracer was also preferentially retained at LepR pericytes, we pharmacologically targeted regulators of inter-endothelial junction tightness and found that they affect LepR neuronal signaling and food intake. Optical imaging in MBH slices revealed a long-lasting, tonic calcium increase in LepR pericytes in response to leptin, suggesting pericytic contraction and vessel constriction. Together, our data indicate that LepR pericytes facilitate localized, paracellular blood-brain barrier leaks, enabling MBH LepR neurons to access circulating leptin.
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