A major regulator of body composition, energy balance and food intake is leptin, an adipocytokine. Leptin circulates and has direct actions in the brain and skeletal muscle by binding to the B isoform of leptin receptor (LEPR-B). While there are actions of leptin on other cell types, such as on immune cells and endothelial cells, these are most likely not directly relevant to energy balance. Leptin action in the hypothalamus has proven to be complex. There are numerous hypothalamic nuclei that are responsive to leptin and each of these nuclei has numerous types of neurons, as defined by their neurotransmitter content. The goals of this proposal are to examine the functional importance of POMC/CART neurons, AGRP/NPY neurons and MCH neurons in mediating the effects of leptin. We have three specific aims that are targeted to these three leptin-regulated neuronal cell types.
Aim 1. Determine the role of AGRP deficiency in restoring normal fertility and mammary gland development to LEPR-B deficient females.
Aim 2. Determine the contribution of AGRP/NPY/GABA transmission from arcuate AGRP neurons to the obesity/diabetes syndrome.
Aim 3. Determine the direct and indirect regulation of MCH neurons by leptin and the significance of this regulation to the obesity/diabetes syndrome. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
3R01DK057621-08S1
Application #
7689012
Study Section
Special Emphasis Panel (ZRG1-EMNR-J (03))
Program Officer
Sato, Sheryl M
Project Start
2000-06-01
Project End
2011-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
8
Fiscal Year
2008
Total Cost
$91,947
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
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Jo, Young-Hwan; Su, Ya; Gutierrez-Juarez, Roger et al. (2009) Oleic acid directly regulates POMC neuron excitability in the hypothalamus. J Neurophysiol 101:2305-16

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