The pathological precursors of cardiovascular disease begin in childhood. This proposal uses the baboon as an animal model to investigate the role of infant overfeeding as a factor leading to adolescent obesity and its association with serum lipids and lipoproteins. It is hypothesized that preweaning overfeeding predisposes the female infant to develop obesity when influenced by a positive energy balance or age and puberty. This hypothesis will be tested by measuring body composition and fat cell size from infancy to puberty in four groups of pedigreed female baboons Group 1-baboons normally fed, Group 2-baboons overfed with a palatable diet from weaning to 1 year, Group 3-baboons overfed with formula from birth to weaning, and Group 4- baboons overfed from birth to 1 year of age. At 1 year all baboons will be fed the same diet. Body composition will be measured using nuclear magnetic resonance determination of total body water, lean and fat mass. Also morphometric measures (crown-rump length, triceps circumference) will be used to monitor changes in lean mass and mean fat cell size and abdominal fat thickness will be used to monitor changes in fat mass. To identify physiological processes associated with infant overfeeding and adolescent obesity we will measure the diurnal rhythm of plasma cortisol, cortisol response to feeding and stress, fasting insulin, and the insulin response to feeding and intravenous glucose challenge. We will also measure adipose tissue lipoprotein lipase activity and insulin stimulated lipogenesis. A suspension cell culture system using methylcellulose will be adapted to the baboon to determine if preadipocytes from overfed infants have a greater capacity for triglyceride accumulation in vitro than preadipocytes from normally fed baboons. Metabolic rate and food intake will be periodically measured to determine if overfed infants have altered energy balance. The hormone, adipose tissue metabolism, metabolic rate, and food intake measurements will be made at weaning and periodically until 3 1/2 years of age in order to determine whether these processes are affected by infant ovrefeeding prior to the development of obesity. Finally, the associated of plasma triglyceride, cholesterol, VLDL + LDL, and HDL with developing obesity will be examined. The main effects of infant diet, sire, and age and the infant diet by sire interaction on all variables will be statistically analyzed.
