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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
3R01DK074046-01A1S1
Application #
7483499
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Miles, Carolyn
Project Start
2007-09-01
Project End
2012-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
1
Fiscal Year
2007
Total Cost
$64,261
Indirect Cost
Name
St. Luke's-Roosevelt Institute for Health Sciences
Department
Type
DUNS #
623216371
City
New York
State
NY
Country
United States
Zip Code
10019
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Carnell, Susan; Benson, Leora; Chang, Ku-Yu Virginia et al. (2017) Neural correlates of familial obesity risk and overweight in adolescence. Neuroimage 159:236-247
Geliebter, Allan; Benson, Leora; Pantazatos, Spiro P et al. (2016) Greater anterior cingulate activation and connectivity in response to visual and auditory high-calorie food cues in binge eating: Preliminary findings. Appetite 96:195-202
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Geliebter, Allan; Krawitz, Emily; Ungredda, Tatiana et al. (2015) Physiological and Psychological Changes Following Liposuction of Large Volumes of Fat in Overweight and Obese Women. J Diabetes Obes 2:1-7
Gluck, Marci E; Yahav, Eric; Hashim, Sami A et al. (2014) Ghrelin levels after a cold pressor stress test in obese women with binge eating disorder. Psychosom Med 76:74-9
Atalayer, Deniz; Pantazatos, Spiro P; Gibson, Charlisa D et al. (2014) Sexually dimorphic functional connectivity in response to high vs. low energy-dense food cues in obese humans: an fMRI study. Neuroimage 100:405-13
Carnell, Susan; Benson, Leora; Pantazatos, Spiro P et al. (2014) Amodal brain activation and functional connectivity in response to high-energy-density food cues in obesity. Obesity (Silver Spring) 22:2370-8
Atalayer, Deniz; Gibson, Charlisa; Konopacka, Alexandra et al. (2013) Ghrelin and eating disorders. Prog Neuropsychopharmacol Biol Psychiatry 40:70-82
Geliebter, Allan (2013) Neuroimaging of gastric distension and gastric bypass surgery. Appetite 71:459-65

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