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: 7737328
• 负责人: ALLAN GELIEBTER
• 金额: $ 55.38万
• 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/7737328
• 关键词: Acetaminophen; Area; Beds; 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; 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; Visual; Vomiting; Weight; Woman; anorexigenic peptide; auditory stimulus; bariatric surgery; comparison group; experience; feeding; frontal lobe; gastrointestinal system; ghrelin; glucagon-like peptide 1; improved; indexing; interest; men; non-diabetic; pandemic disease; peptide hormone; primary outcome; public health relevance; relating to nervous system; response; sensory cortex

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）：肥胖已达到流行病的程度。目前，严重肥胖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 胃绕道手术 (RYGB) 后减少食​​物摄入和减轻体重的机制尚不清楚。本研究利用功能磁共振成像 (fMRI) 和减肥手术前后食欲相关肠肽水平的测量来研究与进餐开始和终止有关的神经和激素机制。参与者将在手术前、手术后 3 个月（体重快速减轻期间）和手术后 18 个月（体重减轻基本稳定时）进行研究。腹腔镜 RYGB 和胃束带 (GB) 两个手术组将与两个对照组：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且不接受任何治疗的参与者 (NT)。功能磁共振成像将用于检查固定膳食后大脑对高适口性食物（HPF）、低适口性食物（LPF）和非食物（NF）视觉和听觉刺激的激活区域。从 RYGB 前到后，为了响应 HPF 刺激，我们预计与食物和奖励相关的关键大脑区域（例如眶额皮质 [OFC]）会最大程度减少，GB 后激活程度减少较少，WL 增加， NT 没有变化。这两种手术都会限制胃的大小，但与 GB 不同的是，RYGB 涉及切开胃并绕过一段肠道。胃的这种切片可能会降低胃产生的促食欲激素胃饥饿素的水平，胃饥饿素与进餐开始有关。此外，肠道绕道术可能会提高餐后促食欲激素 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功能磁共振成像之前的早晨固定流质餐之前、期间和之后 1 小时进行测量。 RYGB 后，餐后肠道肽（所有这些肽都穿过血脑屏障）应进一步有助于减少响应 HPF 刺激的关键奖励区域的大脑激活。我们预计 RYGB 之后 ghrelin 会减少，但 PYY 和 GLP-1 会升高。 GB 组以及在更大程度上 WL 组预计会经历与 RYGB 后所见相反方向的肠道肽变化。作为次要目标，我们将评估暴食行为，预计在 RYGB 后暴食行为将减少最多。我们总共将招募 136 名相对健康（非糖尿病）严重肥胖（BMI = 40-50 kg/m2）的男性和女性，四组每组 34 名参与者。 BMI 范围将确保几乎所有参与者都适合功能磁共振成像扫描仪。所有四个组都将在性别、体重指数和卧床状况方面进行匹配。这项研究的结果应该可以提高我们对减肥手术后促进食欲和减轻体重的生物学机制的认识。这些知识可能会带来非手术替代方案，模仿 RYGB 对神经和荷尔蒙变化的影响，从而导致长期体重减轻。公共卫生相关性：肥胖已成为世界范围内的流行病，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导致体重减轻的机制。将通过两种类型的肥胖手术来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）胃绕道术和2）胃束带术。这两个手术组将与两个非手术对照组进行比较。该研究结果可以更好地解释为什么手术会导致体重显着减轻，并可能改善手术效果。这些发现还可能提高我们对肥胖原因的理解，从而可能带来新的侵入性较小的治疗方法。