Activation of Central Orexin/Hypocretin Neurons by Dietary Amino Acids
Activation of Central Orexin/Hypocretin Neurons by Dietary Amino Acids
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DOI：
10.1016/j.neuron.2011.08.027
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发表时间：
2011-11-17
期刊：
影响因子：
16.2
通讯作者：
Burdakov, Denis
中科院分区：
文献类型：
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作者：
Karnani, Mahesh M.;Apergis-Schoute, John;Burdakov, Denis
下丘脑食欲素/下丘脑分泌素（orx/hcrt）神经元调节能量平衡、清醒和奖励；失去它们会导致嗜睡症和体重增加。葡萄糖可以降低1 /hcrt细胞的活性，但其他饮食常量营养素是否有类似的效果尚不清楚。我们发现orx/hcrt细胞受到营养相关的氨基酸混合物（AAs）的刺激，无论是在脑切片膜片钳实验中，还是在小鼠体内中央或外周给药AAs后的c-Fos表达分析中。通过抑制K（ATP）通道和激活系统- a氨基酸转运体的双重机制，AAs电刺激orx/hcrt细胞的生理混合物。非必需AAs比必需AAs更能激活orx/hcrt细胞。此外，生理浓度的AAs抑制了orx/hcrt细胞的葡萄糖反应。这些结果提示下丘脑整合大量营养素信号的新机制，并暗示orx/hcrt细胞感知细胞外液中的大量营养素平衡，而不是净能量值。
Hypothalamic orexin/hypocretin (orx/hcrt) neurons regulate energy balance, wakefulness, and reward; their loss produces narcolepsy and weight gain. Glucose can lower the activity of one/hcrt cells, but whether other dietary macronutrients have similar effects is unclear. We show that orx/hcrt cells are stimulated by nutritionally relevant mixtures of amino acids (AAs), both in brain slice patch-clamp experiments, and in c-Fos expression assays following central or peripheral administration of AAs to mice in vivo. Physiological mixtures of AAs electrically excited orx/hcrt cells through a dual mechanism involving inhibition of K(ATP) channels and activation of system-A amino acid transporters. Nonessential AAs were more potent in activating orx/hcrt cells than essential AAs. Moreover, the presence of physiological concentrations of AAs suppressed the glucose responses of orx/hcrt cells. These results suggest a new mechanism of hypothalamic integration of macronutrient signals and imply that orx/hcrt cells sense macronutrient balance, rather than net energy value, in extracellular fluid.