Obesity is estimated to effect 15% of American children; however, a specific etiology can be identified in only a very small fraction of these children. Although the determinants of childhood obesity are multifactorial (genetic, overeating, physical activity, etc.), the influence of nutritional modifications during early childhood as an etiology of obesity later in life is poorly understood. Animal models for investigation of the influence of nutritional modifications on the development of obesity are limited only to either overnourishment during the suckling period or premature weaning of suckling rat pups (beginning on day 16) on a diet high in carbohydrate (CHO) instead of rat milk (high in fat). Artificial rearing of rat pups (using intragastric cannulation) presents a unique approach to examine both the short-term and the long-lasting effects of early nutritional modifications (feeding a milk formula high in CHO instead of rat milk which is high in fat) on CHO and lipid metabolism. Our hypothesis is that the consumption of a formula high in CHO alters the hormonal and metabolic responses not only during the 'suckling' period but also later in adult life. We have observed hyperinsulinemia in rat pups while they were artificially reared on the high-CHO milk-formula. Our preliminary results show that this group of rats grew heavier and also had increased lipogenic capacities in liver and adipose tissues later in adult life compared to corresponding parameters in age-matched rats reared naturally. Newborn rats will be fitted with intragastric cannulas and fed milk-substitute formulas high in either CHO-derived or fat-derived calories. The latter group will serve as an experimental control. Naturally reared rats will also be included as an additional control. We will investigate the proliferation of pancreatic cells, and proliferation and differentiation rates of stromal vascular (preadipocytes) cells into mature adipocytes using morphometric analysis and pulse- labeling of DNA, and changes in cell size and number during the postnatal period. Basal levels of plasma hormones and lipids, and hormonal secretory responses and lipogenesis will be studied. Possible influence of additional nutritional modifications (such as diets high in sucrose or fat) during adult life on long-lasting effects will be similarly investigated. This study has important implications for the development of obesity and altered metabolic response to nutritional modifications imposed in early childhood.