Functional Brain Imaging and Appetite-Related Hormones Pre and Post Obesity Surge

描述（由申请人提供）：肥胖已达到流行病的比例。目前，严重肥胖症的唯一有效的长期治疗方法是减肥手术。然而，肥胖手术，特别是鲁昂-Y胃旁路术（RYGB）后减少食物摄入和体重减轻的机制还不清楚。本研究利用功能性磁共振成像（fMRI）和减肥手术前后食欲相关的肠肽水平的测量，以研究开始和终止进餐所涉及的神经和激素机制。将在术前、术后3个月对受试者进行研究（快速体重减轻期间）和术后18个月两个手术组，腹腔镜RYGB和胃束带（GB），将与两个对照组进行比较：i）通过3个月配方饮食减肥的参与者（WL），以及ii）符合条件但选择不接受手术和不接受治疗的参与者（NT）。fMRI将用于检查固定膳食后对高适口性食物（HPF）、低适口性食物（LPF）和非食物（NF）的视觉和听觉刺激的脑激活区域。从RYGB前到后，在对HPF刺激的反应中，我们预计与食物和奖励相关的关键脑区（如眶额皮质[OFC]）的减少最大，GB后激活减少较少，WL增加，NT没有变化。这两种手术都限制了胃的大小，但与GB不同的是，RYGB涉及切除胃并绕过一段肠。胃的这种切片可能会降低胃产生的食欲激素生长激素释放肽的水平，这与进餐开始有关。此外，肠旁路术可能会升高餐后促氧化激素PYY和GLP-1的水平，这些激素与进餐终止有关。这些与食欲相关的激素将在fMRI前的早晨固定液体餐之前、之前和之后1小时进行测量。在RYGB之后，餐后肠道肽，所有这些都穿过血脑屏障，应该有助于进一步减少响应HPF刺激的关键奖励区域的大脑激活。我们预计，减少饥饿素，但升高PYY和GLP-1，以下RYGB。预计GB组和WL组在更大程度上经历与RYGB后观察到的方向相反的肠肽变化。作为第二个目标，我们将评估暴饮暴食行为，预计在RYGB后减少最多。总共，我们将招募136名相对健康（非糖尿病）的严重肥胖（BMI = 40-50 kg/m2）男性和女性，四组各34名参与者。BMI范围将确保几乎所有参与者都适合fMRI扫描仪。所有四个组将在性别、BMI和BED状态方面进行匹配。这项研究的结果应该提高我们对减肥手术后有助于食欲和体重减轻的生物学机制的认识。这一知识可能会导致非手术替代方案，模拟RYGB对神经和激素变化的影响，导致长期减肥。公共卫生相关性：肥胖症已经成为一种世界性的流行病，与此同时，针对严重肥胖者的减肥手术数量急剧增加。本研究的目的是更好地了解肥胖手术导致体重减轻的机制。将在两种类型的肥胖手术后评估大脑对食物刺激的反应的变化以及消化系统产生的食欲激素的变化：1）胃旁路术和2）胃束带术。将这两个手术组与两个非手术对照组进行比较。这项研究结果可能更好地解释了为什么手术会导致体重明显减轻，并可能导致手术的改进。这些发现也可能提高我们对肥胖原因的理解，这可能导致新的侵入性较小的治疗方法。

DESCRIPTION (provided by applicant): Obesity has reached pandemic proportions. Currently, the only effective long term treatment for severe obesity is bariatric surgery. However, the mechanisms of reduced food intake and weight loss after obesity surgery, particularly Rouen-Y gastric bypass (RYGB), are not well understood. This study utilizes functional magnetic resonance imaging (fMRI) and measures of appetite-related gut peptide levels pre and post bariatric surgery to investigate the neurological and hormonal mechanisms involved in initiation and termination of meals. Participants will be studied prior to surgery, 3 mo post surgery (during rapid weight loss), and 18 mo post surgery (when weight loss has generally stabilized).Two surgical groups, laparoscopic RYGB and gastric banding (GB), will be compared to two control groups: i) participants losing weight on a 3-mo formula diet (WL), and ii) those who qualify for, but choose not to undergo surgery and receive no treatment (NT). fMRI will be used to examine areas of brain activation in response to visual and auditory stimuli of high- palatability foods (HPF), low-palatability foods (LPF), and non-foods (NF) following a fixed meal. From pre to post RYGB, in response to HPF stimuli, we anticipate the greatest reduction in key brain areas associated with food and reward (such as the orbitofrontal cortex [OFC]), a lesser reduction in activation after GB, an increase in WL, and no change in NT. Both surgical operations restrict the size of the stomach but, unlike GB, RYGB involves sectioning the stomach and bypassing a segment of the intestine. This sectioning of the stomach may reduce levels of the orexigenic hormone ghrelin, produced by the stomach, which is involved in meal initiation. In addition, the intestinal bypass may elevate postprandial levels of the anorexigenic hormones, PYY and GLP-1, which are involved in meal termination. These appetite-related hormones will be measured prior to, through, and 1 hour after, a morning fixed liquid meal just before the fMRI. After RYGB, the postprandial gut peptides, all of which cross the blood-brain barrier, should contribute further to reducing brain activation in key reward areas in response to HPF stimuli. We anticipate a decrease in ghrelin, but elevated PYY and GLP-1, following RYGB. The GB group and, to a greater extent, the WL group are expected to experience gut peptide changes opposite in direction to those seen following RYGB. As a secondary aim, we will assess binge eating behavior, which is expected to diminish the most after RYGB. Altogether, we will enroll 136 relatively healthy (non-diabetic) severely obese (BMI = 40-50 kg/m2) men and women, with 34 participants in each of the four groups. The BMI range will ensure that virtually all participants will fit into the fMRI scanner. All four groups will be matched for gender, BMI, and BED status. The findings from the study should improve our knowledge of the biological mechanisms that contribute to appetite and weight reduction after bariatric surgery. This knowledge may lead to non-surgical alternatives that mimic the effects of RYGB on neurological and hormonal changes that result in long-term weight loss. PUBLIC HEALTH RELEVANCE: Obesity has become a world-wide epidemic, and at the same time the number of bariatric surgeries for severely obese people has increased dramatically. The objective of this study is to better understand the mechanisms by which obesity surgery causes weight loss. Changes in brain responses to food stimuli as well as changes in appetite hormones produced by the digestive system will be assessed following two types of obesity surgery: 1) gastric bypass and 2) gastric banding. These two surgical groups will be compared to two non-surgical control groups. The study findings may better explain why surgery results in marked weight loss and may lead to improved operations. The findings may also improve our understanding of the causes of obesity, which could lead to new less invasive treatments.