NEUROPEPTIDE Y--EFFECTS ON ENERGY METABOLISM

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The brain's critical role in regulating energy and fat balance has never been more apparent. Several recent developments (see (l)) have focused attention on brain regulatory systems: leptin, the product of the ob gene, appears to signal fat status to the brain; the tubby gene appears to code for a protein expressed in hypothalamus; and a new satiety- inducing neuroregulator GLP-1 and feeding stimulator, melanocyte- concentrating hormone have been found to work in hypothalamus. It is evident that abnormalities in brain regulatory mechanisms may be responsible for alterations in energy balance (obesity, anorexia, etc.) in animals and in humans. Neuropeptide Y (NPY) is the most potent known neuroregulator of appetite and can be used, as described herein, to functionally map one brain system regulating energy balance (appetite and energy metabolism), which in this proposal we will call the Neuropeptide Y-Coded Energy Management Network (NEMN). The goal of these investigations is to define the central organization of one brain system regulating energy balance (appetite and energy metabolism), which in this proposal we will call the Neuropeptide Y-Coded Energy Management Network (NEMN). Abnormalities and disturbances in NEMN regulatory mechanisms could be responsible for alterations in energy balance (obesity, anorexia, etc.) in animals and in humans. Neuropeptide Y (NPY) is the most potent known orexigenic agent. We will utilize NPY administration into the hypothalamic paraventricular nucleus as the primary tool to functionally map the circuitry of the NEMN. We hypothesize a distributed energy management network in the brain, which can be traced using the stimulus of NPY. OBJECTIVES: (1) Define the neuronal sites activated by NPY in hypothalamic paraventricular nucleus, opioids in nucleus of the solitary tract, and by food deprivation through examining site specific expression of the immediate early gene, c-fos; (2) Verify the functional efferent link between NPY activity in the PVN and opioidergic activity in the NTS: (3) Functionally define the next circuit projections for the NPY-Coded Energy Management Network, (4) Define the site of action and regulatory significance of serotonin blockade of NPY effects on energy metabolism.