The attainment of energy balance and a healthy body weight requires coordinated, bi-directional communication between the central nervous system and sites outside the brain, including both white and brown adipose tissue (BAT). This grant proposal will integrate and extend emerging information on the mechanisms by which peripheral signals, including those central neural regulators of energy balance, to maintain normal function, or produce disease. A major finding from the initial funding period of this grant project was the discovery that BAT deficiency produced by a transgenic toxigene caused obesity by a mechanisms that included both efficient metabolism and increased food intake. The first specific aim will attempt to determine the mechanisms within the brain by which BAT deficiency produces this unexpected effect on food intake. Since the BAT deficient mice that the PI created do not have total BAT deficiency, and it would be very valuable to have totally BAT deficient mice, the second specific aim will endeavor to create, by a novel strategy, mice with total absence of BAT for additional studies of the function of this tissue. Studies during the previous period revealed the existence of signals from the hormone whose absence results in profound obesity.
The third aim will determine the central mechanisms by which these leptin-independent signals influence energy intake and expenditure. It is apparent that the central regulation of energy balance requires the coordinated action of a number of neuropeptides and neurotransmitter, important among which are NPY, melanin concentrating hormone (MCH), agouti related peptide (AgRP), and products of the proopiomelanocortin (POMC) gene. In the fourth aim, the investigators will use transgenic and gene targeting approaches involving several of these genes to ask questions about the mechanisms by which they function together to regulate energy balance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK046930-09
Application #
6380820
Study Section
Nutrition Study Section (NTN)
Program Officer
Yanovski, Susan Z
Project Start
1993-08-01
Project End
2003-07-31
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
9
Fiscal Year
2001
Total Cost
$311,992
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
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