Regulation of Brain Signaling After Bariatric Surgery

减肥手术后大脑信号的调节

• 批准号: 8038527
• 负责人: JONATHAN Q. PURNELL
• 金额: $ 15万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-21 至 2011-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8038527
• 关键词: Adipocytes; Adipose tissue; Affect; Alleles; Americas; Amygdaloid structure; Animal Model; Attenuated; Bariatrics; Behavior; Behavior Control; Behavioral; Binding; Binge Eating; Blood; Body Composition; Body Weight; Body Weight decreased; Brain; Brain Stem; Brain imaging; Clinical; Communication; Corpus striatum structure; Cross-Sectional Studies; DRD2 gene; Diet; Dopamine D2 Receptor; Dorsal; Eating; Eating Behavior; Eating Disorders; Endocrine system; Energy Metabolism; Food; Functional Magnetic Resonance Imaging; Future; Gastric Bypass; Genetic Polymorphism; Genotype; Goals; Homeostasis; Hormonal; Hormones; Human; Hunger; Hypothalamic structure; Image; Impairment; Infusion procedures; Intake; Leptin; Link; Measures; Mechanics; Modeling; Monitor; Morbidity - disease rate; Motivation; Nerve; Neuraxis; Neurologic; Obesity; Operative Surgical Procedures; Overweight; Pancreatic Polypeptide; Participant; Pathway interactions; Patients; Physiological; Physiology; Procedures; Protocols documentation; Regulation; Reporting; Resolution; Rewards; Role; Saline; Satiation; Scanning; Scientist; Signal Transduction; Solutions; Stimulus; Subgroup; Testing; Time; Visual; Weight; Weight Gain; alternative treatment; analog; bariatric surgery; blood oxygenation level dependent response; clinical decision-making; constriction; experience; follow-up; frontal lobe; ghrelin; increased appetite; insight; leptin receptor; mortality; obesity treatment; programs; receptor; response; reward circuitry; visual stimulus; weight loss intervention

Animal models have provided insight into the physiology of weight regulation, including the hormonal and neurological communication between adipose tissue, the gut, and the brain. Adipocyte hormones, such as leptin, and gut hormones, such as ghrelin, control meal-related food intake and energy expenditure through mechanisms that include direct binding to receptors in the brain stem and brain, and by altering afferent vagal signaling. Recent imaging studies in humans recording brain responses to visual and gustatory food stimuli have consistently demonstrated involvement of dopaminergic pathways traditionally linked with reward motivation. With the discovery of leptin receptors within these pathways, a more integrated model of central nervous system control of food intake is emerging. Most of the imaging reports to date, however, have been cross-sectional studies that have compared obese to lean subjects. Only a few have measured brain responses to changes in levels of hormones involved in weight regulation, such as leptin, and only one studied patients after weight loss. Because of counter regulatory hormonal control, sustained weight loss is difficult to achieve in obese subjects despite intensive behavioral strategies. Bariatric surgery, however, achieves meaningful sustained weight loss, but the mechanisms for this are poorly understood. Thus, the overall goal for this project is to bring together clinical scientists with expertise in brain imaging and the physiological and behavioral control of food intake to better understand the role and interaction of changes in the sensitivity of the brain to hormonal signaling and response to external food stimuli following bariatric surgery. Subjects about to undergo either gastric bypass, gastric banding, or a low-calorie diet weight loss program will complete fMRI paradigms assessing BOLD activation of brain reward circuitry in response to food intake and food images under three different infusion conditions: leptin, ghrelin, and saline. They will also complete measures of body composition, visual analog scores for hunger and satiety, and adlibitum food intake. Participants will then return two more times after surgery to repeat this assessment protocol to determine if these bariatric procedures differentially impact BOLD response of reward circuitry to hormonal and food stimuli and whether this responsivity predicts subsequent weight loss. Finally, subgroups with polymorphisms of the dopamine D2 receptor and those with persistent binge eating behavior are hypothesized to be less responsive to effects of hormonal manipulation on brain fMRI response, to surgically induced weight loss, and will be more likely to regain weight during long-term follow-up. This project will provide new insights into mechanisms leading to sustained weight loss that involve brain centers regulating body weight and attempt to identify subgroups that are responders or non-responders following bariatric surgery.

动物模型提供了对体重调节生理学的深入了解，包括激素调节。 以及脂肪组织、肠道和大脑之间的神经交流。脂肪细胞激素，如 瘦素和肠激素，如胃饥饿素，通过以下途径控制与膳食相关的食物摄入和能量消耗： 这些机制包括直接与脑干和大脑中的受体结合，以及通过改变传入迷走神经， 发信号。人类对视觉和味觉食物刺激的脑反应的最新成像研究 一直以来都证明了多巴胺能神经通路与奖赏有关 动机随着瘦素受体在这些通路中的发现，一个更完整的中枢模型， 神经系统对食物摄入的控制正在出现。然而，迄今为止的大多数成像报告都是 比较肥胖和消瘦受试者的横断面研究。只有少数人测量过大脑 对参与体重调节的激素水平变化的反应，如瘦素，只有一项研究 患者减肥后由于反调节激素的控制，持续减肥是很难的， 在肥胖受试者中实现，尽管强化行为策略。减肥手术，然而， 有意义的持续减肥，但其机制知之甚少。 因此，该项目的总体目标是将具有脑领域专业知识的临床科学家聚集在一起， 成像和食物摄入的生理和行为控制，以更好地了解作用， 大脑对激素信号的敏感性变化和对外部食物刺激的反应的相互作用 在减肥手术后。受试者即将接受胃旁路术、胃束带术或低热量 饮食减肥计划将完成功能磁共振成像范例评估BOLD激活大脑奖励电路， 在三种不同输注条件下对食物摄入和食物图像的反应：瘦素、生长激素释放肽和盐水。 他们还将完成身体成分的测量，饥饿感和饱腹感的视觉模拟评分以及随意性 食物摄入量参与者将在手术后再次返回两次以重复此评估 方案，以确定这些减肥程序是否差异影响奖励电路的BOLD反应， 激素和食物刺激，以及这种反应性是否预示着随后的体重减轻。最后，Subgroups 多巴胺D2受体多态性和持续暴食行为的患者， 假设对激素操纵对大脑功能磁共振成像反应的影响反应较低， 诱导体重减轻，并且在长期随访期间更有可能恢复体重。该项目将 为持续减肥的机制提供了新的见解， 体重，并尝试确定肥胖治疗后的应答者或非应答者亚组 手术