Changes in neural response to eating after bariatric surgery: MRI results

描述（由申请人提供）：减肥手术是极端肥胖者最有效的减肥选择（即，体重指数= 40 kg/m2）。Roux-en-Y胃旁路术（RYGB）和腹腔镜可调节胃束带术（LAGB）是最常见的减肥手术，它们分别导致初始体重长期减少约25%和约15%。两种手术导致的解剖学差异与术后内分泌功能的差异有关。特别是，食欲素，胃饥饿素，通常在RYGB中受到抑制，在LAGB患者中增加。此外，与LAGB相比，RYGB后饱腹感因子、胰高血糖素样肽1（GLP-1）和肽YY（PYY 3 -36）的餐后增加显著增加。这些调节食欲的激素中的每一种都被发现在与食物摄入的自我平衡和享乐控制相关的大脑区域中起作用。另一篇文献研究了进食中心的神经激活，通过功能性磁共振成像（fMRI）和正电子发射断层扫描（PET）进行测量，以响应食物提示。这些研究中的大多数都比较了对高热量与低热量食物或非食物的图像的反应。有些人进一步比较了瘦与肥胖个体的反应。通常，高热量食物图像刺激前额叶皮层、中脑边缘多巴胺系统（例如，腹侧被盖区和脑桥核），和其它边缘区（例如，眶额皮质、杏仁核、杏仁核和扣带皮质）。此外，肥胖个体的反应比瘦个体的反应更大。很少有研究研究考察对膳食消耗的神经反应;这些研究发现，许多相同的区域会因营养摄入而激活。 拟议的研究是一项前瞻性观察性研究，旨在整合两个调查领域：1）减肥手术的内分泌影响; 2）对食物线索和喂养的神经反应。接受RYGB或LAGB的患者，以及不寻求减肥的匹配肥胖对照组，将在0、6和18个月时完成评估访视，其中包括：1）在禁食状态下观察高热量和低热量食物图像时进行fMRI扫描; 2）在禁食状态下进行灌注MRI扫描以测量脑血流量; 3）空腹抽血; 4）消耗液体测试餐; 5）连续灌注MRI扫描以评估膳食的影响;和5）连续抽血以评估胃饥饿素、GLP-1和PYY 3 -36的餐后变化。在6个月和18个月随访时比较三组之间的变化将构成我们的主要分析。主要假设是手术后：1）与LAGB患者和对照组相比，RYGB患者对高热量食物图像的fMRI反应将降低; 2）RYGB患者餐后GLP-1和PYY 3 -36将显示更大的增加。（伴有餐后生长激素释放肽反应减弱）;和3）RYGB患者将比LAGB和对照参与者表现出更大的餐后稳态和享乐进食区的静息脑活动增加。 公共卫生相关性：这项研究是一项为期18个月的前瞻性观察性研究，研究对象是寻求腹腔镜可调节胃束带术（LAGB）或Roux-en-Y胃旁路术（RYGB）手术的极度肥胖患者。使用功能和灌注磁共振成像，我们将评估手术后6个月和18个月对食物提示和膳食摄入的神经反应的变化。两种手术方法的变化将相互比较，并与一组不寻求减肥的极度肥胖者进行比较。此外，我们将连续测量餐后食欲调节激素的变化，并检查神经和内分泌反应之间的关系，以食物消费。

DESCRIPTION (provided by applicant): Bariatric surgery is the most effective weight loss option for persons with extreme obesity (i.e., body mass index = 40 kg/m2). Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) are the most common bariatric procedures, and they induce long-term reductions of ~25% and ~15% of initial weight, respectively. Anatomical differences resulting from the two procedures are associated with postoperative differences in endocrine functioning. In particular, the orexigenic hormone, ghrelin, is generally suppressed in RYGB and increased in LAGB patients. Furthermore, postprandial increases in the satiety factors, glucagon-like peptide 1 (GLP-1) and peptide YY (PYY3-36), are significantly increased after RYGB, compared with LAGB. Each of these appetite-regulating hormones has been found to act in brain regions related to both the homeostatic and hedonic control of food intake. A separate literature has examined neural activation in feeding centers, as measured with functional magnetic resonance imaging (fMRI) and positron emitted tomography (PET), in response to food cues. Most of these studies have compared responses to images of high-calorie vs. low-calorie foods or non-food items. Some have further compared responses in lean vs. obese individuals. Generally, high-calorie food images stimulate activation in the prefrontal cortex, mesolimbic dopamine system (e.g., ventral-tegmental area and nucleus accumbens), and other limbic areas (e.g., orbitofrontal cortex, amygdala, insula, and cingulate cortex). Furthermore, responses are greater in obese vs. lean individuals. Fewer studies have examined neural response to meal consumption; those investigations have found that many of the same regions are activated by nutrient ingestion. The proposed research is a prospective observational study that seeks to integrate two areas of inquiry: 1) endocrine effects of bariatric surgery; and 2) neural response to food cues and feeding. Patients who undergo RYGB or LAGB, and matched obese controls who do not seek weight loss, will complete assessment visits at 0, 6, and 18 months, which include: 1) a fMRI scan while viewing high- and low-calorie food images in the fasted state; 2) a perfusion MRI scan to measure cerebral blood flow in the fasted state; 3) fasting blood draw; 4) consumption of a liquid test meal; 5) serial perfusion MRI scans to assess the effects of the meal; and 5) serial blood draws to assess postprandial changes in ghrelin, GLP-1, and PYY3-36. Comparisons of changes among the three groups at 6-months and 18-months follow-up will comprise our primary analyses. The primary hypotheses are that following surgery: 1) fMRI response to high-calorie food images will be reduced in RYGB vs. LAGB patients and controls; 2) RYGB patients will show larger increases in postprandial GLP-1 and PYY3-36 (accompanied with a blunted postprandial ghrelin response) than will LAGB patients and controls; and 3) RYGB patients will demonstrate a greater postprandial increase in resting brain activity in homeostatic and hedonic feeding areas than will LAGB and control participants. PUBLIC HEALTH RELEVANCE: The proposed research is an 18-month prospective observational study of extremely obese patients who seek laparoscopic adjustable gastric banding (LAGB) or roux-en-Y gastric bypass (RYGB) surgery. Using functional and perfusion magnetic resonance imaging, we will assess changes in neural response to food cues and meal ingestion 6 and 18 months after surgery. Changes in the two surgical approaches will be compared with each other and with those in a group of extremely obese individuals who do not seek weight loss. In addition, we will serially measure postprandial changes in appetite-regulating hormones and examine the relationships between neural and endocrine response to food consumption.