Date

April 2011

Document Type

Dissertation

Degree Name

Ph.D.

Institution

Oregon Health & Science University

Abstract

Along with an increasing prevalence of adult obesity world wide, an increasing prevalence of obesity and its co-morbidities has also been documented in children. Diseases once only normally found in adults are occurring with greater frequency in pediatric populations. Type 2 diabetes mellitus as well as secondary co-morbidities such as hypertension, non-alcoholic fatty liver disease, hyperlipidemia, and metabolic syndrome are now becoming increasingly common in children. While associations between maternal obesity (without diabetes) or weight gain during pregnancy and childhood obesity have been suggested, the contributions of these conditions to fetal programming are not well understood. However, it is clear from studies in both humans and rodents that intra partum and early postnatal environments are critical to the development of systems that regulate body weight, energy and glucose homeostasis. Seminal work in humans highlighted the effects that the intrauterine environment has on the development of adult cardiovascular disease, hypertension and bronchitis in cases of maternal undernutrition. While malnutrition is certainly still pervasive in our world today, modern industrialized societies are also suffering from overnutrition and obesity at epidemic rates. Our work is focused on understanding the effects that overnutrition and obesity have on developing children. While work with rodents has provided much information, there are important species-specific differences between rodents and humans that preclude translation of rodent findings directly into human obesity research. The nonhuman primate model of maternal overnutrition utilized in this dissertation was chosen for the similarities that exist in development between the nonhuman primate and humans. We believe the studies described in this dissertation will extend our current knowledge of hepatic nervous system development in the nonhuman primate, an area of research that has not been well characterized. In addition, our findings have important clinical implications for understanding how maternal nutrition impacts human development. Human studies based on our findings in the nonhuman primate are currently underway. Our model is a tremendous resource that will allow us, as well as other investigators, to implement rigorous explorations into the effects that obesity and/or a high fat diet have on the growing epidemic of human obesity; a disease whose prevention may have to begin even before conception.

Identifier

doi:10.6083/M4KW5D1C

Division

Neuroscience Graduate Program

School

School of Medicine

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