The long-term effects of early under-and overfeeding on glucose metabolism and fat cell lipogenesis were studied. Newborn rats were reared in litter sizes of four, 10, and 16 pups. The amount of milk intake per pup varied inversely with litter sizes. A subgroup of pups from each group was studied at age 20 d, whereas another subgroup was weaned to an ad libitum feeding of standard rat chow and studied at 12 wk of age. There were no differences among groups in food intake on the basis of per gram body weight. Overfeeding during suckling resulted in fatter rats at weaning and in the adults. The higher fat contents in the adipose tissues and carcasses were associated with higher fatty acid synthase and lipogenic activities in the adipose tissues at weaning and 12 wk of age. Differences in plasma insulin and glucose levels among groups were observed only in the 20-d-old rats: basal insulin and glucose levels and 30-min postglucose insulin levels were highest in the overnourished and lowest in the undernourished rats. However, by 12 wk of age, there were no significant differences among groups in their basal insulin and glucose levels and after an oral dose of glucose. Our results suggest that overfeeding or underfeeding during the suckling period affects the glucose-insulin axis only temporarily and not permanently, but early overfeeding permanently enhances fatty acid synthase and lipogenic activities in adipose tissues, resulting in fatter adult rats. Abbreviations FAS, fatty acid synthase RSA, relative specific activity Persistent impairment of insulin secretion and glucose tolerance has been observed after refeeding in malnourished infants (1) and in rats subjected to protein-calorie (2) and protein (3) malnutrition. On the other hand, overfeeding rats during the suckling period was associated with hyperinsulinemia in infancy and impaired glucose tolerance and obesity in the adult (4). Enlarged adipocytes biopsied from obese adult humans showed decreased sensitivity to insulin action (5), an effect proposed as one of the factors influencing insulin secretion (6).In rats, the level of FAS, an enzyme that catalyzes de novo synthesis of fatty acid, declines during fasting and increases during refeeding. These changes in FAS levels have been attributed to an insulin-stimulated transcription of FAS in the liver and adipose tissues (7), a proposal supported by the findings that incubation of human adipocytes with insulin increases FAS activity (8). It has also been reported that the expression of FAS in mice can be altered by dietary composition (9). This may explain the increase in the mRNA concentrations and activities of lipogenic enzymes such as FAS and acetyl CoA-carboxylase in rats during weaning (10, 11).In experimental animals, it has been shown that either underfeeding or overfeeding during early infancy confers a lasting effect on body fat content (12). However, whether this is a direct consequence of changes in insulin levels and lipogenic enzyme activities is not known. We postulate that early postnatal nu...