Defining the Role of Cholecystokinin in the Lipid-Induced Human Brain Activation Matrix
Defining the Role of Cholecystokinin in the Lipid-Induced Human Brain Activation Matrix
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DOI：
10.1053/j.gastro.2009.12.060
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发表时间：
2010-04-01
期刊：
影响因子：
29.4
通讯作者：
Thompson, David George
中科院分区：
文献类型：
--
作者：
Lassman, Daniel J.;Mckie, Shane;Thompson, David George
背景与目的：在人类中，在大多数脊椎动物中，通过摄入食物释放肠肽胆囊收缩素（CCK）在消化和进一步食物摄入的调节中起着重要作用，但脑功能的变化及其潜在的激活机制仍然未知。我们的目的是探索，使用一种新的生理磁共振成像方法，时空大脑激活矩阵，在响应摄入的脂肪餐，并通过使用CCK-1受体拮抗剂，以确定CCK在这种激活的作用。方法：我们研究了，在19名健康受试者，脑激活反应摄入脂质（十二烷酸）或盐水（对照）与磁共振成像。同时记录胆囊体积、血浆CCK水平和主观饥饿感和饱胀感评分。然后重复实验，使用和不使用CCK-1受体拮抗剂右氧戊酰胺（600 mg口服），采用对照、随机顺序、拉丁方设计。研究结果：摄入的脂质激活了双侧大脑区域的基质，特别是脑干、脑桥、下丘脑以及小脑和运动皮质区。这些激活被右氧葡胺消除，表明CCK介导的途径，独立于任何营养相关的意识线索。结论：这些激活的识别现在定义了脂质激活的大脑基质，并提供了一种手段，通过这种手段，可以区分来自肠道的食物调节的自我平衡机制，从次要的感觉和享乐的线索，从而提供了一种新的方法来探索异常的人类胃肠道反应和饮食行为。
BACKGROUND & AIMS: In human beings, as in most vertebrates, the release of the intestinal peptide cholecystokinin (CCK) by ingested food plays a major role both in digestion and the regulation of further food intake, but the changes in brain function and their underlying activation mechanisms remain unknown. Our aim was to explore, using a novel physiologic magnetic resonance imaging approach, the temporospatial brain activation matrix, in response to ingestion of a lipid meal and, by use of a CCK-1 receptor antagonist, to define the role of CCK in this activation. METHODS: We studied, in 19 healthy subjects, the brain activation responses to ingested lipid (dodecanoic acid) or saline (control) with magnetic resonance imaging. Gallbladder volume, plasma CCK levels, and subjective hunger and fullness scores were also recorded. The experiment was then repeated, with and without prior administration of the CCK-1 receptor antagonist dexloxiglumide (600 mg orally) with a controlled, randomized order, latin-square design. RESULTS: Ingested lipid activated bilaterally a matrix of brain areas, particularly the brain stem, pons, hypothalamus, and also cerebellum and motor cortical areas. These activations were abolished by dexloxiglumide, indicating a CCK-mediated pathway, independent of any nutrient-associated awareness cues. CONCLUSION: The identification of these activations now defines the lipid-activated brain matrix and provides a means by which the gut-derived homeostatic mechanisms of food regulation can be distinguished from secondary sensory and hedonic cues, thereby providing a new approach to exploring aberrant human gastrointestinal responses and eating behavior.