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

肥胖激增前后的功能性脑成像和食欲相关激素

• 批准号: 8146066
• 负责人: ALLAN GELIEBTER
• 金额: $ 53.13万
• 依托单位: ST. LUKE'S-ROOSEVELT INST FOR HLTH SCIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-09 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8146066
• 关键词: Acetaminophen; Area; Binge Eating; Biological; Blood; Blood - brain barrier anatomy; Body Weight; Body Weight decreased; Brain; Brain imaging; Brain scan; Bypass; Control Groups; Desire for food; Disease; Eating; Eating Behavior; Eating Disorders; Enrollment; Ensure; Epidemic; Exhibits; Fasting; Food; Formula Diets; Frequencies; Functional Magnetic Resonance Imaging; Gastric Bypass; Gastric Emptying; Gender; Health; Homeostasis; Hormonal; Hormonal Change; Hormones; Hour; Hunger; Hypothalamic structure; Intervention; Intestinal Bypasses; Intestines; Knowledge; Lead; Limb structure; Liquid substance; Measures; Morbid Obesity; Motor; Neurologic; Obesity; Operative Surgical Procedures; Participant; Patients; Pattern; Peptide YY; Peptides; Phase; Physiological; Plasma; Prefrontal Cortex; Prevalence; Pylorus; Qualifying; Regulation; Relative (related person); Rewards; Satiation; Signal Transduction; Specific qualifier value; Stimulus; Stomach; Symptoms; Testing; Time; Tracer; Vomiting; Weight; Woman; anorexigenic peptide; auditory stimulus; bariatric surgery; comparison group; experience; feeding; frontal lobe; gastrointestinal system; ghrelin; glucagon-like peptide; improved; indexing; interest; men; non-diabetic; operation; pandemic disease; peptide hormone; primary outcome; relating to nervous system; response; sensory cortex; visual stimulus

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.

描述（由申请人提供）：肥胖已达到大流行比例。目前，严重肥胖症的唯一有效的长期治疗方法是减肥手术。但是，尚不清楚肥胖手术后的食物摄入量和体重减轻的机制，尤其是Rouen-Y胃旁路（RYGB）的机制尚不清楚。这项研究利用功能性磁共振成像（fMRI）以及与食欲相关的肠道肽水平前和减肥手术后的测量方法，以研究参与餐食起始和终止的神经系统和激素机制。参与者将在手术前进行手术前3个月（快速减肥）和手术后18个月（通常稳定体重稳定时）。两个手术组，腹腔镜Rygb和胃带（GB）（GB）（GB），将与两个对照组相比，将参与者与3-MO饮食相比，并与3 MO饮食相比（WL）和II的疗法（WL）和II的疗效（WL）相比（nt）。 fMRI将用于检查固定餐后，响应高古rapitability食品（HPF），低估计性​​食品（LPF）和非食品（NF）的视觉和听觉刺激，以检查大脑激活区域。从雷格布（RYGB）前到后，响应于HPF刺激，我们预计与食物和奖励相关的关键大脑区域的减少最大（例如Orbitrontal Cortex [OFC]），GB后激活的降低较小，WL的增加，NT不变。两项手术手术都限制了胃的大小，但是与GB不同，RYGB涉及切片胃并绕过肠的一部分。胃切片可能会降低由胃部产生的甲素激素生长素的水平，该水平参与饮食开始。此外，肠旁路可能会升高参与饮食终止的厌食激素，PYY和GLP-1的餐后水平。这些与食欲相关的荷尔蒙将在frmi之前，早晨固定液体餐之前，再到1小时之前测量。在RYGB之后，餐后肠道肽（所有越过血脑屏障）应进一步促进响应HPF刺激的关键奖励区域的脑激活。我们预计RYGB后，生长素释放蛋白会减少，但PYY和GLP-1升高。 GB组，在更大程度上，WL组有望经历与RYGB后看到的方向相反的肠道肽的变化。作为次要目的，我们将评估暴饮暴食行为，这预计在RYGB之后会减少最大的饮食行为。总的来说，我们将招募136名相对健康的（非糖尿病）严重肥胖（BMI = 40-50 kg/m2）的男性和女性，这四个组中的每一组都有34名参与者。 BMI系列将确保几乎所有参与者都适合FMRI扫描仪。所有四个小组都将符合性别，BMI和床位状态。研究结果应提高我们对减肥手术后食欲和体重减轻的生物学机制的了解。这些知识可能导致非手术替代方法模仿RYGB对导致长期体重减轻的神经和激素变化的影响。公共卫生相关性：肥胖已成为全球流行病，同时，严重肥胖者的减肥手术数量急剧增加。这项研究的目的是更好地了解肥胖手术会导致体重减轻的机制。在两种类型的肥胖手术后，将评估大脑对食物刺激的反应变化以及消化系统产生的食欲激素的变化：1）胃旁路和2）胃伴侣。这两个手术组将与两个非手术对照组进行比较。研究结果可以更好地解释为什么手术会导致体重显着，并可能导致手术改善。这些发现还可以提高我们对肥胖原因的理解，这可能导致新的侵入性治疗。