Arcuate NPY Controls Sympathetic Output and BAT Function via a Relay of Tyrosine Hydroxylase Neurons in the PVN
Arcuate NPY Controls Sympathetic Output and BAT Function via a Relay of Tyrosine Hydroxylase Neurons in the PVN
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DOI：
10.1016/j.cmet.2013.01.006
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发表时间：
2013-02-05
期刊：
影响因子：
29
通讯作者：
Lin, Shu
中科院分区：
文献类型：
--
作者：
Shi, Yan-Chuan;Lau, Jackie;Lin, Shu
神经肽Y（NPY）以其强大的刺激食物摄入和减少能量消耗的作用而闻名。然而，所涉及的途径和背后的调控机制还不清楚。在这里，我们证明，神经肽Y来自弓状核（弧）是至关重要的交感神经流出和棕色脂肪组织（BAT）功能的控制。从机制上讲，Arc NPY信号传导诱导的一个关键变化是Y1受体介导的下丘脑室旁核（PVN）中酪氨酸羟化酶（TH）表达的显着减少，这也与蓝斑（LC）中TH表达的减少有关。和其他区域在脑干中。与此一致，Arc NPY信号降低交感神经支配的BAT产热，涉及BAT中解偶联蛋白1（UCP 1）表达的下调。综上所述，这些数据揭示了一个强大的Arc-NPY调节的神经元回路，通过TH神经元控制BAT产热和交感神经输出。
Neuropepetide Y (NPY) is best known for its powerful stimulation of food intake and its effects on reducing energy expenditure. However, the pathways involved and the regulatory mechanisms behind this are not well understood. Here we demonstrate that NPY derived from the arcuate nucleus (Arc) is critical for the control of sympathetic outflow and brown adipose tissue (BAT) function. Mechanistically, a key change induced by Arc NPY signaling is a marked Y1 receptor-mediated reduction in tyrosine hydroxylase (TH) expression in the hypothalamic paraventricular nucleus (PVN), which is also associated with a reduction in TH expression in the locus coeruleus (LC) and other regions in the brainstem. Consistent with this, Arc NPY signaling decreased sympathetically innervated BAT thermogenesis, involving the downregulation of uncoupling protein 1 (UCP1) expression in BAT. Taken together, these data reveal a powerful Arc-NPY-regulated neuronal circuit that controls BAT thermogenesis and sympathetic output via TH neurons.