Leptin is the primary signal of energy stores that is perceived by the brain. Yet little is known about how leptin acts on the brain to carry that signal of peripheral fat levels. We have identified part of the mechanism that leptin uses to signal to brain cells. At least one of the major targets of leptin is a group of cells in the hypothalamus, these cells secrete a-MSH, a neuropeptide known to inhibit feeding and to increase energy expenditure. We propose that another target of leptin will be those hypothalamic neurons that secrete NYP, a neuropeptide that increases feeding and decreases energy expenditure. Furthermore, we propose that leptin will act in the opposite way on NPY neurons, it will inhibit them. We will determine the actions of leptin on POMC and NPY/AGRP neurons by measuring their electrical activity in response to leptin treatment. The different neurons will be visually identified by the targeted (transgenic) expression of 2 different colored fluorescent proteins. We will determine how the leptin receptor can have such different actin is the two neuronal populations by analyzing the signal transduction pathways used by leptin in each type of neuron, and the ion channels that are modulated in each class of neuron. We will attempt to show that these neurons are a major way that leptin """"""""informs"""""""" the brain about adipose stores, and we will determine if this leptin signal is changed in situations when leptin has different effect to its normal role.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK062202-05
Application #
7067190
Study Section
Endocrinology Study Section (END)
Program Officer
Sato, Sheryl M
Project Start
2002-08-15
Project End
2007-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
5
Fiscal Year
2006
Total Cost
$290,463
Indirect Cost
Name
Oregon Health and Science University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
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