| Summary: | Thesis (Ph.D.)--Memorial University of Newfoundland, 2009. Biochemistry Includes bibliographical references (leaves 209-224) Epidemiological studies have consistently indicated that low birth weight is associated with increased risks of chronic diseases in adulthood. Due to limitations of human studies, various animal models are used to elucidate the mechanisms regulating developmental programming of chronic adult diseases. A large proportion (80-90%) of the human incidence of intrauterine growth restriction, resulting in low birth weight, is may be due to impaired nutrient perfusion through the placenta. Spontaneous low birth weight animal models also represent placental insufficiency and may be appropriate models for the human. The overall objective of this thesis was to determine whether the spontaneous naturally occurring low birth weight (i.e., runt) Yucatan miniature pig represents a suitable model for studying developmental origins of chronic adult diseases by investigating biological markers of obesity and cardiovascular diseases. The runts showed qualities similar to low birth weight infants, i.e., small size at birth, an increased rate of postnatal growth (catch-up growth), and organ and metabolic changes which led to the development of obesity and early indicators of cardiovascular diseases. Specifically, runts experienced catch-up growth (prior to sexual maturity at 7 mo old). The catch-up growth was partly due to increased feed intake, which was independent of the post-weaning diet provided, suggesting developmental programming of food intake regulation. Catch-up growth was also associated with increased adiposity in the runts. Furthermore, blood pressure was inversely related to birth weight, similar to findings in epidemiological studies. The higher blood pressure in the runts was significantly correlated to lower nephron number. The results showed that low birth weight was associated with a dyslipidaemic plasma profile as indicated by the higher plasma triglyceride levels in the runts in both the fasted and postprandial states. Finally, a post-weaning dietary intake also plays an important role as a determinant of chronic disease outcomes; a post-weaning Western-style diet that was high in salt, fat and sugar exacerbate early programming of blood pressure and lipid profile in the runts. Overall, the Yucatan miniature swine has many attributes for a good animal model to explore mechanisms that contribute to the developmental origins of human adult chronic diseases.
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