The incidence of preventable metabolic diseases in children has increased markedly over the past 2 decades. Currently, there is little information to determine the underlying causes or whether therapeutic or dietary interventions might be successful at preventing or reducing metabolic health risks in children from obese pregnancies. While studies in rodents have demonstrated that both maternal and perinatal nutritional environment is critical for normal development of the offspring, these are a short lived species with a different developmental pattern than primates. These studies will use a nonhuman primate (NHP) model to investigate the impact of poor maternal metabolic health and diet on the long-term health of the offspring up to adolescence. This will be the first study use a NHP model to investigate the long-term susceptibility to diet induced obesity and diabetes caused by poor maternal metabolic health and diet. For these studies, breeding NHPs will be chronically maintained on a diet high in fats and calories (HFD), similar to the typical American diet. The NHP is a critical model as it shares developmental features similar to human fetuses, especially in relationship to the brain. This proposal will focus on the impact on brain neurocircuitry that are critical for regulating energy expenditure as well as homeostatic and hedonic (reward) based feeding behavior. The hypothesis is that abnormalities in the development of this neurocircuitry lead to inappropriate metabolic compensatory responses to various metabolic challenges. Furthermore, we expect that HFD offspring will have a more potent drive to consume palatable and calorically dense foods. It is also hypothesized that these HFD offspring will display accelerated weight gain and insulin resistance when maintained chronically on a HFD during adolesecence, resulting in an early onset of metabolic complications (i.e., obesity and insulin resistance). Consumption of tasty and calorie dense foods is a major underlying cause of childhood obesity. These studies will determine if the drive to consume these foods is programmed during fetal development by the diet that the mother is consuming during pregnancy. Furthermore, these studies will identify potential long- term metabolic risks caused by this early reprogramming.
Poor maternal health and nutrition are associated with an increased risk of metabolic diseases in children. However, the underlying complications and mechanisms that lead to the increase in obesity and diabetes in children are poorly understood. The NHP is a critical model to identify these mechanisms because of the similarities in development, as well as the structure and function of metabolic systems.
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