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. Infant and juvenile obesity is a rising epidemic within the U.S. While this increase has been attributed to many factors, most notably increased caloric intake and decreased exercise, we argue that the prenatal environment may be a critical period for establishing the homeostatic mechanisms that will regulate food intake and glucose homeostasis during childhood and into adulthood. Therefore, poor maternal health (i.e., obesity and diabetes) and diet may predispose the offspring to metabolic imbalances resulting in early onset obesity/diabetes. The species difference in the development of metabolic systems makes it critical that a nonhuman primate (NHP) model is developed to study metabolic disorders that occur during development. The purpose of these studies is to use a NHP model to determine what defects are caused in the body weight/adiposity regulatory systems of the offspring of dams with gestational diabetes and obesity. The specific purposes of this research consortium are: 1) Determine the metabolic disturbances in offspring from mothers with gestational hyperinsulinemia/hyperleptinemia. 2) Determine if maternal obesity/diabetes causes abnormalities in the development of hypothalamic feeding circuits in NHP offspring. 3) Identify and characterize POMC neurons in macaques using lentoviral transfection with a POMC-GFP construct. 4) Determine the development of hypothalamic circuits in humans. 5) Determine the tissue-specific mechanisms of imprinting fetal insulin resistance and obesity. 6) Determine if maternal obesity/diabetes causes abnormalities in the development of synapses in NHP offspring. We expect that this multidisciplinary research team will be able to identify the site of the metabolic disturbances caused by maternal obesity/diabetes. Since these studies will be performed in a NHP model, the results will be directly applicable to humans. Furthermore, we will develop new tools, classically used only in rodents, for the use in NHP.
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