Peptide YY directly inhibits ghrelin-activated neurons of the arcuate nucleus and reverses fasting-induced c-Fos expression
Peptide YY directly inhibits ghrelin-activated neurons of the arcuate nucleus and reverses fasting-induced c-Fos expression
复制标题
DOI：
10.1159/000079842
复制
发表时间：
2004-01-01
影响因子：
4.1
通讯作者：
Lutz, TA
中科院分区：
文献类型：
--
作者：
Riediger, T;Bothe, C;Lutz, TA
下丘脑弓状核（Arc）监测和整合参与维持能量稳态的激素和代谢信号。胃促生长素（ghrelin）是大鼠胃在能量摄入为负状态时分泌的一种促氧肽，它直接激活大鼠内侧弓状核（ArcM）神经元。与胃饥饿素相反，肽YY （PYY）在餐后从肠道释放，并在外周应用时减少食物摄入量。ArcM中的神经元表达生长素受体和神经肽Y受体。因此，PYY可能通过作用于饥饿激素敏感的Arc神经元来抑制摄食。利用细胞外记录，我们(1)表征了PYY对大鼠ArcM中胃饥饿素敏感神经元电活动的影响。为了将PYY对神经元活动的影响与能量状态联系起来，我们(2)研究了PYY对小鼠Arc神经元中禁食诱导的c-Fos表达的逆转能力。此外，我们(3)试图确认PYY在我们的实验条件下减少食物摄入量。PYY的灌注可通过直接的突触后机制可逆地抑制94%的ArcM神经元。PYY诱导的抑制是剂量依赖性的，发生在10-8 m的阈值浓度，与胃饥饿素和PYY对食物摄入的相反作用一致，高百分比（50%）的Arc神经元被胃饥饿素激活而被PYY抑制。与这种抑制作用一致，外周注射PYY部分逆转了小鼠Arc神经元中禁食诱导的c-Fos表达。同样地，重新喂食被剥夺食物的老鼠可以逆转禁食引起的Arc激活。此外，外周注射PYY减少了禁食12小时小鼠的食物摄入量。由此可见，小鼠Arc神经元的活性与摄食状态相关，不仅摄食降低了Arc神经元的活性，而且PYY也降低了Arc神经元的活性。总之，我们目前的观察结果表明，PYY可能通过抑制Arc神经元来促进能量摄入的积极状态，而Arc神经元在能量摄入的消极状态下被ghrelin等信号激活。版权所有(C) 2004 S. Karger AG，巴塞尔。
The hypothalamic arcuate nucleus ( Arc) monitors and integrates hormonal and metabolic signals involved in the maintenance of energy homeostasis. The orexigenic peptide ghrelin is secreted from the stomach during negative status of energy intake and directly activates neurons of the medial arcuate nucleus (ArcM) in rats. In contrast to ghrelin, peptide YY (PYY) is released postprandially from the gut and reduces food intake when applied peripherally. Neurons in the ArcM express ghrelin receptors and neuropeptide Y receptors. Thus, PYY may inhibit feeding by acting on ghrelin-sensitive Arc neurons. Using extracellular recordings, we ( 1) characterized the effects of PYY on the electrical activity of ghrelin-sensitive neurons in the ArcM of rats. In order to correlate the effect of PYY on neuronal activity with the energy status, we ( 2) investigated the ability of PYY to reverse fasting-induced c-Fos expression in Arc neurons of mice. In addition, we ( 3) sought to confirm that PYY reduces food intake under our experimental conditions. Superfusion of PYY reversibly inhibited 94% of all ArcM neurons by a direct postsynaptic mechanism. The PYY-induced inhibition was dose-dependent and occurred at a threshold concentration of 10-8 M. Consistent with the opposite effects of ghrelin and PYY on food intake, a high percentage (50%) of Arc neurons was activated by ghrelin and inhibited by PYY. In line with this inhibitory action, peripherally injected PYY partly reversed the fasting-induced c-Fos expression in Arc neurons of mice. Similarly, refeeding of food-deprived mice reversed the fasting-induced activation in the Arc. Furthermore, peripherally injected PYY reduced food intake in 12-hour fasted mice. Thus the activity of Arc neurons correlated with the feeding status and was not only reduced by feeding but also by administration of PYY in non-refed mice. In conclusion, our current observations suggest that PYY may contribute to signaling a positive status of energy intake by inhibiting Arc neurons, which are activated under a negative status of energy intake by signals such as ghrelin. Copyright (C) 2004 S. Karger AG, Basel.