This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Obesity is a worldwide health concern, being a major contributor to the increased incidence of coronary heart disease and type II diabetes. In 1998, 18% of the adults in the United States were defined as being obese, with twice that number being overweight. Even more disturbing is the dramatic increase in obesity and type II diabetes among children. The central hypothesis of this proposal is that body weight management during adulthood is directly determined by the hypothalamic feeding circuits established during a 'critical period' in postnatal development. Furthermore, if exposure to perturbations in energy balance occur during this 'critical period' of neural plasticity, permanent alterations in body weight management may occur. One of the most potent modulators of appetite in the brain is neuropeptide Y (NPY). There are dynamic changes in the hypothalamic NPY system during development and this system plays a role in regulation of energy homeostasis during this important growth phase. This proposal will study the postnatal period to 1) Determine the functional importance of the development of ARH projections. 2) Determine if NPY plays a role in the regulation of energy balance during the early postnatal period. 3) Determine if changes in the NPY system are responsible for the obese phenotype induced by chronic postnatal overfeeding. The main goal of this proposal is to use a multidisciplinary approach to determine if modifications of the endogenous NPY system during postnatal development lead to abnormal body weight management during adulthood. These studies will provide important insight into the consequences of manipulation of the NPY feeding circuits, during the postnatal period on metabolic rate and body weight during childhood. Understanding the development of this circuitry is critical to determining the mechanisms that underlie early onset obesity and identifying a critical period for possible intervention.
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