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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD023327-03
Application #
3323441
Study Section
Nutrition Study Section (NTN)
Project Start
1987-09-01
Project End
1992-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Southwest Foundation for Biomedical Research
Department
Type
DUNS #
City
San Antonio
State
TX
Country
United States
Zip Code
78245
Lewis, D S; Jackson, E M; Mott, G E (1995) Triiodothyronine accelerates maturation of bile acid metabolism in infant baboons. Am J Physiol 268:E889-96
Lewis, D S; DeChant, D; deLemos, R A (1993) Effect of premature birth and survival on hepatic thyroxine 5'-monodeiodinase activity in baboons. J Clin Endocrinol Metab 76:902-6
Lewis, D S; Soderstrom, P G (1993) In vivo and in vitro development of visceral adipose tissue in a nonhuman primate (Papio species). Metabolism 42:1277-83
Lewis, D S; Jackson, E M; Mott, G E (1992) Effect of energy intake on postprandial plasma hormones and triglyceride concentrations in infant female baboons (Papio species). J Clin Endocrinol Metab 74:920-6
Lewis, D S; Coelho Jr, A M; Jackson, E M (1991) Maternal weight and sire group, not caloric intake, influence adipocyte volume in infant female baboons. Pediatr Res 30:534-40
Lewis, D S; Jackson, E M (1990) Feeding influences plasma cortisol levels during preweaning life in baboons. Am J Physiol 259:R157-62
Lewis, D S; Bertrand, H A; McMahan, C A et al. (1989) Influence of preweaning food intake on body composition of young adult baboons. Am J Physiol 257:R1128-35
Lewis, D S; Mott, G E; McMahan, C A et al. (1988) Deferred effects of preweaning diet on atherosclerosis in adolescent baboons. Arteriosclerosis 8:274-80