Appetite Hormones in Binge Eating Disorder

描述（由申请人提供）：肥胖在全球范围内的流行率持续增加。相当大一部分肥胖受试者患有暴食症（BED），并且摄入大量食物，而没有清除神经性贪食症。BED是最常见的饮食失调症，会造成许多痛苦和痛苦。还有一组未充分研究的瘦床个体，有肥胖的风险。通过包括它们，BED的病理生理学可以与肥胖分开。BED的心理学方面比生物学方面得到了更好的研究。在初步研究中，影响食欲的激素存在差异，特别是刺激食欲的ghrelin，在固定的早餐前ghrelin水平较低，在肥胖的BED受试者中之后下降幅度较小。这一发现是违反直觉的，因为ghrelin预计会更高。这是可能的，胃饥饿素，自然增加了一天，是更高的床上比非床上个人在晚上时，大多数暴饮暴食发生。在固定的晚间测试餐后，床上的ghrelin也应该有较小的下降，这可能导致更多的后续食物摄入。在36名BED和36名非BED受试者中，按体重和性别平均分配，将在早晨和晚上固定餐后2小时内研究食欲相关激素，包括胃饥饿素和饱腹感肽、GLP-1和PYY。然后受试者可自由进食直至吃饱。预计在床上摄入量会更大，特别是在晚上。将在另一天应用社会压力协议（特里尔），以提高这些受试者的皮质醇。预计在BED中，与更大的饥饿和膳食摄入相关的皮质醇反应增强。这种BED病理生理学模型假定了进餐开始（晚上较高的ghrelin和应激源后较高的皮质醇）和进餐终止（较低的GLP-1，PYY，特别是在晚上）的异常。接下来，将在研究2中实施几种最有希望的急性干预措施：a）阻断皮质醇产生，以及B）PYY或c）GLP-1给药。这些研究应该有助于揭示BED的病理生理学，并通过纠正潜在的食欲-激素模式紊乱，确定是什么维持了这种紊乱，并为新药治疗提供基础。公众：这项研究的重点是食欲激素，可能维持暴食症（BED），常见于肥胖的人。然后，我们将尝试纠正最不正常的食欲激素，以测试一种新的药物治疗方法。

DESCRIPTION (provided by applicant): Obesity continues to increase in prevalence worldwide. A sizable subset of obese subjects has binge eating disorder (BED), and ingest large meals, without the purging of bulimia nervosa. BED, the most common eating disorder, causes much suffering and distress. There is also a group of understudied lean BED individuals, at risk for obesity. By including them, the pathophysiology of BED can be parceled from obesity. The psychological aspects of BED have been better studied than the biological aspects. In preliminary studies, there were differences in hormones influencing appetite, especially ghrelin, which stimulates appetite, with lower ghrelin levels before a fixed morning meal and a smaller decline afterwards in obese BED subjects. This finding was counterintuitive because ghrelin was expected to be higher. It is possible that ghrelin, which naturally increases over the day, is higher in BED than in non-BED individuals in the evening when most binge eating occurs. Following a fixed evening test meal, there should also be a smaller decline in ghrelin in BED, which may lead to more subsequent food intake. In 36 BED and 36 non-BED subjects, equally divided by weight and gender, appetite-related hormones, will be studied, including ghrelin, and the satiety peptides, GLP-1, and PYY, during 2 hours after a fixed meal in the morning and in the evening. Subjects will then have an ad libitum meal until full. The intake is expected to be greater in BED, especially in the evening. A social stress protocol (Trier) will be applied on another day to raise cortisol in these subjects. An enhanced cortisol response associated with greater hunger and meal intake is expected in BED. This model of BED pathophysiology posits abnormalities in both meal initiation (higher ghrelin in evening, and higher cortisol following a stressor) and in meal termination (lower GLP-1, PYY, especially in evening). Next, the most promising of several acute interventions: a) blocking cortisol production, and either b) PYY, or c) GLP-1 administration, will be implemented in Study 2. These studies should help reveal BED pathophysiology, and by correcting a potential disordered appetite-hormone pattern, determine what maintains the disorder, and provide a basis for new drug treatments. Public: This study focuses on appetite hormones that may maintain binge eating disorder (BED), common in obese individuals. We will then attempt to correct the most abnormal appetite hormone to test a new drug treatment approach in BED.