Obesity, continues to increase in prevalenceworldwide. A sizable subset of obese subjects has binge eating disorder (BED), and ingest large meals, without the purging of bulimia nervosa. BED, the mostcommon 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 pathophysiologyof 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 hormonesinfluencing appetite, especially ghrelin, which stimulates appetite, with lower ghrelin levels before a fixed morning meal and a smaller decline afterwardsin 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 BEDthan 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 expectedto 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 asociated 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), commonin obese individuals. We will then attempt to correct the most abnormal appetite hormone to test a new drug treatment approach in BED.
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