The nucleus tractus solitarius: a portal for visceral afferent signal processing, energy status assessment and integration of their combined effects on food intake
The nucleus tractus solitarius: a portal for visceral afferent signal processing, energy status assessment and integration of their combined effects on food intake
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DOI：
10.1038/ijo.2009.10
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发表时间：
2009-04-01
影响因子：
4.9
通讯作者：
Hayes, M. R.
中科院分区：
文献类型：
--
作者：
Grill, H. J.;Hayes, M. R.
对于人类和动物模型，普遍认为中枢神经系统对摄取的食物产生的胃肠道(GI)信号的处理提供了进餐数量和频率的主要决定因素。尽管如此，相对较少的研究旨在描绘介导胃肠道刺激诱导的摄入抑制的大脑回路、神经化学通路和细胞内信号。最近又出现了两个追求这些电路和信号的动机。首先，胃旁路手术在肥胖治疗中的成功突出了胃肠信号的作用，如胰高血糖素样肽-1(GLP-1)在摄取和能量平衡控制中的作用。其次，越来越多的数据表明，瘦素的摄入量减少效应可能是通过放大GI信号的摄入量抑制效应来调节的。实验表明：(1)外周给药的GLP-1受体激动剂的摄食抑制效应是由尾侧脑干神经元介导的，这种作用不需要前脑-下丘脑的神经处理；(2)许多对胃扩张有反应的孤束内侧核(NTS)神经元也是由瘦素驱动的；(3)以脑干为靶标的尾侧瘦素能增强胃扩张和肠道营养刺激的摄食抑制效应；(4)富含NTS的脑组织裂解物中的AMPK活性在食物缺乏时升高，在再摄食时降低。(5)后脑导向的瘦素的摄取抑制作用可通过提高后脑AMPK活性而逆转。总体而言，数据支持这样的观点，即NTS和后脑内的回路介导了GI信号的摄取抑制，瘦素对食物摄取的影响是通过GI信号处理的放大而产生的。《国际肥胖杂志》(2009年)33，S11-S15；DOI：10.1038/ijo.2009.10
For humans and animal models alike there is general agreement that the central nervous system processing of gastrointestinal (GI) signals arising from ingested food provides the principal determinant of the size of meals and their frequency. Despite this, relatively few studies are aimed at delineating the brain circuits, neurochemical pathways and intracellular signals that mediate GI-stimulation-induced intake inhibition. Two additional motivations to pursue these circuits and signals have recently arisen. First, the success of gastric-bypass surgery in obesity treatment is highlighting roles for GI signals such as glucagon-like peptide-1 (GLP-1) in intake and energy balance control. Second, accumulating data suggest that the intake-reducing effects of leptin may be mediated through an amplification of the intake-inhibitory effects of GI signals. Experiments reviewed show that: (1) the intake-suppressive effects of a peripherally administered GLP-1 receptor agonist is mediated by caudal brainstem neurons and that forebrain-hypothalamic neural processing is not necessary for this effect; ( 2) a population of medial nucleus tractus solitarius (NTS) neurons that are responsive to gastric distention is also driven by leptin; ( 3) caudal brainstem-targeted leptin amplifies the food-intake-inhibitory effects of gastric distention and intestinal nutrient stimulation; (4) adenosine monophosphate-activated protein kinase (AMPK) activity in NTS-enriched brain lysates is elevated by food deprivation and reduced by refeeding and ( 5) the intake-suppressive effect of hindbrain-directed leptin is reversed by elevating hindbrain AMPK activity. Overall, data support the view that the NTS and circuits within the hindbrain mediate the intake inhibition of GI signals, and that the effects of leptin on food intake result from the amplification of GI signal processing. International Journal of Obesity (2009) 33, S11-S15; doi:10.1038/ijo.2009.10