Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding.
Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding.
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DOI：
10.1038/nn.3725
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发表时间：
2014-07
影响因子：
25
通讯作者：
Horvath, Tamas L.
中科院分区：
文献类型：
--
作者：
Kim, Jae Geun;Suyama, Shigetomo;Koch, Marco;Lin, Sungho;Argente-Arizon, Pilar;Argente, Jesus;Liu, Zhong-Wu;Zimmer, Marcelo R.;Jeong, Jin Kwon;Szigeti-Buck, Klara;Gao, Yuanqing;Garcia-Caceres, Cristina;Yi, Chun-Xia;Salmaso, Natalina;Vaccarino, Flora M.;Chowen, Julie;Diano, Sabrina;Dietrich, Marcelo O.;Tschoep, Matthias H.;Horvath, Tamas L.
我们已经证明，在体外，对代谢变化做出反应的下丘脑喂养回路的突触重组涉及星形胶质细胞，星形胶质细胞可以直接对代谢激素瘦素做出反应。目前尚不清楚胶质细胞在下丘脑突触适应中的作用是主动的还是被动的。在这里，我们发现瘦素受体在下丘脑星形胶质细胞中表达，成人有条件地删除星形胶质细胞中的瘦素受体会导致胶质细胞形态改变，胶质覆盖率降低，并增加对阿片黑素皮质素原(POMC)和Agti相关蛋白(AgRP)产生神经元的突触输入。在星形胶质细胞特异性瘦素受体缺陷的小鼠中，瘦素诱导的摄食抑制被减弱，而禁食或给予Ghrelin后的反弹摄食增加。这些数据揭示了神经胶质细胞在启动下丘脑突触可塑性和神经内分泌控制瘦素摄食中的积极作用。
We have shown that synaptic re-organization of hypothalamic feeding circuits in response to metabolic shifts involves astrocytes, cells that can directly respond to the metabolic hormone, leptin, in vitro. It is not known whether the role of glia cells in hypothalamic synaptic adaptions is active or passive. Here we show that leptin receptors are expressed in hypothalamic astrocytes and that conditional, adult deletion of leptin receptors in astrocytes leads to altered glial morphology, decreased glial coverage and elevated synaptic inputs onto pro-opiomelanocortin (POMC)- and Agouti-related protein (AgRP)-producing neurons. Leptin-induced suppression of feeding was diminished, while rebound feeding after fasting or ghrelin administration was elevated in mice with astrocyte-specific leptin receptor deficiency. These data unmask an active role of glial cells in the initiation of hypothalamic synaptic plasticity and neuroendocrine control of feeding by leptin.
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影响因子：
16.2
作者：
Cowley, MA;Smith, RG;Horvath, TL
通讯作者：
Horvath, TL
影响因子：
16.2
作者：
Vong L;Ye C;Yang Z;Choi B;Chua S Jr;Lowell BB
通讯作者：
Lowell BB
影响因子：
4.8
作者：
García-Cáceres C;Fuente-Martín E;Burgos-Ramos E;Granado M;Frago LM;Barrios V;Horvath T;Argente J;Chowen JA
通讯作者：
Chowen JA
影响因子：
64.5
作者：
Yang, Yunlei;Atasoy, Deniz;Sternson, Scott M.
通讯作者：
Sternson, Scott M.
影响因子：
15.9
作者：
Fuente-Martin, Esther;Garcia-Caceres, Cristina;Chowen, Julie A.
通讯作者：
Chowen, Julie A.