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(即体重指数=40公斤/平方米)最有效的减肥选择。Roux-en-Y胃分流术(RYGB)和腹腔镜可调胃束带术(LAGB)是最常见的减肥术，它们的长期减重效果分别为初始体重的25%和15%。两种手术在解剖学上的差异与术后内分泌功能的不同有关。特别是，促食欲激素Ghrelin在RYGB患者中通常受到抑制，而在LAGB患者中则增加。此外，与LAGB相比，RYGB组餐后饱腹感因子--胰升糖素样肽1(GLP-1)和YY(PYY3-36)显著增加。这些调节食欲的荷尔蒙中的每一种都被发现作用于大脑中与食物摄入量的平衡和享乐控制相关的区域。另有一篇文献研究了喂养中心的神经激活，通过功能磁共振成像(FMRI)和正电子发射断层扫描(PET)测量，对食物提示做出反应。这些研究中的大多数都比较了对高卡路里食物和低卡路里食物或非食物图片的反应。一些人进一步比较了瘦子和肥胖者的反应。一般来说，高卡路里的食物图像会刺激前额叶皮质、中脑边缘多巴胺系统(例如，腹侧被盖区和伏隔核)以及其他边缘区域(例如，眶前叶皮质、杏仁核、脑岛和扣带回皮质)的激活。此外，肥胖者的反应比苗条的人更强烈。较少的研究考察了对进食的神经反应；这些研究发现，营养摄入激活了许多相同的区域。 这项拟议的研究是一项前瞻性的观察性研究，试图整合两个领域的研究：1)减肥手术的内分泌效应；2)对食物提示和喂养的神经反应。接受RYGB或LAGB的患者，以及匹配的不寻求减肥的肥胖对照组，将在0、6和18个月完成评估访问，其中包括：1)在观看禁食状态下高卡路里和低卡路里食物图像的同时进行fMRI扫描；2)灌注MRI扫描以测量禁食状态下的脑血流量；3)空腹抽血；4)摄入液体试餐；5)连续灌注MRI扫描以评估进餐的效果；以及5)连续抽血以评估餐后Ghrelin、GLP-1和PY3-36的变化。比较三组在6个月和18个月随访时的变化将构成我们的初步分析。基本假设是：1)与LAGB患者和对照组相比，RYGB患者和对照组对高热量食物图像的功能磁共振反应将降低；2)与LAGB患者和对照组相比，RYGB患者餐后GLP-1和PYY3-36(伴有迟钝的餐后GRELIN反应)的增加更大；以及3)RYGB患者餐后在稳态和享乐进食区的静息脑活动比LAGB和对照组更大。 公共卫生相关性：这项拟议的研究是一项为期18个月的前瞻性观察研究，对象是寻求腹腔镜可调节胃束带(LAGB)或Roux-en-Y胃旁路(RYGB)手术的极度肥胖患者。使用功能和灌注磁共振成像，我们将在术后6个月和18个月评估神经对食物提示和进食的反应的变化。这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端肥胖者进行比较。此外，我们将连续测量餐后食欲调节荷尔蒙的变化，并研究神经和内分泌对食物消费的反应之间的关系。

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.