Ghrelin raises [Ca2+]i via AMPK in hypothalamic arcuate nucleus NPY neurons
Ghrelin raises [Ca2+]i via AMPK in hypothalamic arcuate nucleus NPY neurons
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DOI：
10.1016/j.bbrc.2007.11.166
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发表时间：
2008-02-08
影响因子：
3.1
通讯作者：
Yada, Toshihiko
中科院分区：
文献类型：
--
作者：
Kohno, Daisuke;Sone, Hideyuki;Yada, Toshihiko
胃饥饿素，一种促食欲激素，直接激活下丘脑弓状核（ARC）中的神经肽Y（NPY）神经元，从而刺激食物摄入。下丘脑的腺苷酸活化蛋白激酶（AMPK）水平（一种细胞内能量传感器）可通过外周和中枢给予胃饥饿素而被激活。我们研究了胃饥饿素是否调节弓状核中NPY神经元的AMPK活性。从弓状核分离单个神经元，通过呋喃-2微量荧光测定法测量胞质Ca2 +浓度（[Ca2 +]（i）），随后对NPY、磷酸化AMPK和磷酸化乙酰辅酶A羧化酶（ACC）进行免疫细胞化学鉴定。胃饥饿素和AICAR（一种AMPK激活剂）增加了从弓状核分离的神经元中的[Ca2 +]（i）。对胃饥饿素起反应的神经元与对AICAR起反应的神经元高度重叠。对胃饥饿素和AICAR都有反应的神经元主要是NPY免疫反应性神经元。用胃饥饿素处理增加了AMPK和ACC的磷酸化。一种AMPK抑制剂，化合物C，抑制了胃饥饿素诱导的[Ca2 +]（i）增加。这些结果表明，胃饥饿素通过弓状核NPY神经元中AMPK介导的信号传导增加[Ca2 +]（i）。（C）2007爱思唯尔公司。保留所有权利。
Ghrelin. an orexigenic hormone, directly activates neuropeptide (NPY) neurons in the hypothalamic arcuate nucleus (ARC), and thereby stimulates food intake. The hypothalamic level of AMP-activated protein kinase (AMPK), an intracellular energy sensor, is activated by peripheral and central administration of ghrelin. We examined whether ghrelin regulates AMPK activity in NPY neurons of the ARC. Single neurons were isolated from the ARC and cytosolic Ca2(+) concentration ([Ca2+](i)) was measured by fura-2 microfluorometry, followed by immunocytochemical identification of NPY, phospho-AMPK, and phospho-acetyl-CoA carboxylase (ACC). Ghrelin and AICAR. an AMPK activator, increased [Ca2+](i) in neurons isolated from the ARC. The ghrelin-responsive neurons highly overlapped with AICAR-responsive neurons. The neurons that responded to both ghrelin and AICAR were primarily NPY-immunoreactive neurons. Treatment with ghrelin increased phosphorylation of AMPK and ACC. An AMPK inhibitor, compound C, suppressed ghrelin-induced [Ca2(divided by)]i increases. These results demonstrate that ghrelin increases [Ca2+](i) via AMPK-mediated signaling in the ARC NPY neurons. (C) 2007 Elsevier Inc. All rights reserved.