Obesity and type 2 diabetes are world wide health issues and their incidence is rapidly increasing. Currently the biological factors responsible for the development of obesity are only partially understood. Recent research has shown that maternal nutrition during pregnancy may have long-term metabolic consequences in offspring. In the present study we investigated interactions between prenatal and postnatal nutrition on leptin sensitivity and obesity development. Wistar rats were time-mated and randomly assigned to either ad-libitum (AD) or to 30% of ad-libitum (UN) food intake throughout pregnancy. After weaning, female offspring were fed standard chow, a high-fat diet or a calorie restricted diet. Female offspring of UN dams were growth retarded at birth and showed increased susceptibility to diet-induced obesity on a high-fat diet. At 142 +/- 5 days of age, leptin sensitivity was measured as a response to 14 days of leptin treatment (2.5 microg/g/day, s.c.). In UN offspring fed chow, leptin treatment failed to reduce food intake and weight loss was diminished. This leptin resistance observed in UN offspring was independent of diet-induced obesity and was associated with fasting hyperinsulinemia and hypertriglyceridemia. Our study suggests that prenatal nutrition can shape future susceptibility to obesity through alterations in leptin sensitivity and changes in energy metabolism during adult life.