AMP-activated protein kinase activates neuropeptide Y neurons in the hypothalamic arcuate nucleus to increase food intake in rats
AMP-activated protein kinase activates neuropeptide Y neurons in the hypothalamic arcuate nucleus to increase food intake in rats
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DOI：
10.1016/j.neulet.2011.05.060
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发表时间：
2011-07-25
影响因子：
2.5
通讯作者：
Yada, Toshihiko
中科院分区：
文献类型：
--
作者：
Kohno, Daisuke;Sone, Hideyuki;Yada, Toshihiko
AMP活化蛋白激酶（AMPK）是一种能量传感器，通过增加细胞内AMP：ATP比率而激活。下丘脑弓状核（ARC）中的AMPK在禁食期间被激活，并且AMPK的激活刺激食物摄入。为了阐明AMPK诱导进食的潜在途径，我们通过用fura-2荧光成像测量胞浆Ca（2+）浓度（[Ca（2+）]（i））来监测单个ARC神经元的活性。AMPK激活剂AICAR-核糖核苷（AICAR）在200 μ M时可增加24% ARC神经元的[Ca（2+）]（i）。在AICAR诱导的[Ca（2+）]（i）反应的神经元中，AMPK和乙酰辅酶A羧化酶被磷酸化。AICAR诱导的[Ca（2+）]（i）增加被无Ca（2+）条件抑制，但不被毒胡萝卜素抑制，表明AICAR通过细胞外间隙的Ca（2+）内流增加[Ca（2+）]（i）。在AICAR反应的ARC神经元中，38%是神经肽Y（NPY）免疫反应神经元，而没有观察到阿黑皮素原（POMC）免疫反应神经元。侧脑室注射AICAR可增加大鼠的摄食量，而联合应用NPY Y1受体拮抗剂1229 U91可消除AICAR诱导的摄食量。这些结果表明AMPK的激活通过Ca（2+）内流导致ARC NPY神经元的激活，从而引起NPY依赖性食物摄取。这些机制可能与生理食欲物质刺激食物摄入有关。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
AMP-activated protein kinase (AMPK) is an energy sensor that is activated by the increase of intracellular AMP:ATP ratio. AMPK in the hypothalamic arcuate nucleus (ARC) is activated during fasting and the activation of AMPK stimulates food intake. To clarify the pathway underlying AMPK-induced feeding, we monitored the activity of single ARC neurons by measuring cytosolic Ca(2+) concentration ([Ca(2+)](i)) with fura-2 fluorescence imaging. An AMPK activator, AICA-riboside (AICAR), at 200 mu M increased [Ca(2+)](i) in 24% of ARC neurons. AMPK and acetyl CoA carboxylase were phosphorylated in the neurons with [Ca(2+)](i) responses to AICAR. AICAR-induced [Ca(2+)](i) increases were inhibited by Ca(2+)-free condition but not by thapsigargin, suggesting that AICAR increases [Ca(2+)](i) through Ca(2+) influx from extracellular space. Among AICAR-responding ARC neurons, 38% were neuropeptide Y (NPY)-immunoreactive neurons while no proopiomelanocortin (POMC)-immunoreactive neuron was observed. Intracerebroventricular administration of AICAR increased food intake, and the AICAR-induced food intake was abolished by the co-administration of NPY Y1 receptor antagonist, 1229U91. These results indicate that the activation of AMPK leads to the activation of ARC NPY neurons through Ca(2+) influx, thereby causing NPY-dependent food intake. These mechanisms could be implicated in the stimulation of food intake by physiological orexigenic substances. (C) 2011 Elsevier Ireland Ltd. All rights reserved.