Obesity is the cause of much morbidity and mortality in the US. Great strides have been made recently in determining the endocrine mechanisms and neuroanatomical pathways that are involved in the development of obesity. One such mechanism involves ghrelin, a hormone that stimulates food intake in animals and whose levels are raised in association with hunger, diet-induced weight loss and certain forms of obesity in humans. The primary purpose of this proposal is to gain a better understanding of ghrelin's role in the regulation of feeding behavior and body weight. The proposed experiments include transgenic and neuroanatomical approaches to determine the central expression patterns of ghrelin's receptor (GHSR), to determine the chemical phenotypes of these ghrelin-responsive neurons and to determine whether these ghrelin-responsive neurons innervate key autonomic, neuroendocrine and behavioral control sites in the brain. Other proposed experiments include disruption of ghrelin's signaling capacity, by deletion of its receptor, to determine if an intact, ghrelin-engaged neuronal circuitry is required for normal body weight homeostasis and the coordinated responses to fasting. Finally, the proposal aims to resolve a debate in the scientific community regarding whether ghrelin is expressed in the brain. We hope that this study will better enable the design of therapeutics to treat and prevent obesity and its co-morbid conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DK064564-01
Application #
6649586
Study Section
Special Emphasis Panel (ZRG1-F06 (20))
Program Officer
Hyde, James F
Project Start
2003-06-01
Project End
2005-05-31
Budget Start
2003-06-01
Budget End
2004-05-31
Support Year
1
Fiscal Year
2003
Total Cost
$56,308
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
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Dhillon, Harveen; Zigman, Jeffrey M; Ye, Chianping et al. (2006) Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron 49:191-203
Zigman, Jeffrey M; Jones, Juli E; Lee, Charlotte E et al. (2006) Expression of ghrelin receptor mRNA in the rat and the mouse brain. J Comp Neurol 494:528-48
Zigman, Jeffrey M; Nakano, Yoshihide; Coppari, Roberto et al. (2005) Mice lacking ghrelin receptors resist the development of diet-induced obesity. J Clin Invest 115:3564-72