Epidemiological studies suggest that maternal undernutrition predisposes individuals to energy balance metabolic development of pathologies in adulthood. Using a model of prenatal maternal 70% food-restricted diet (FR30) in rat, we evaluated peripheral parameters involved in nutritional regulation as well as hypothalamic appetite regulatory system both under resting conditions and following 48 h fasting in adult offspring. Despite comparable glycemia in both groups, FR30 animals had mild glucose intolerance with defect in glucose-induced insulin secretion. They also exhibited hyperleptinemia, while showing similar visible fat deposits. Using semi-quantitative RT-PCR, we observed no basal difference of hypothalamic POMC and NPY gene expression but a decrease of the OB-Rb and an increase of insulin receptor mRNA levels in FR30 animals. They also exhibited basal hypercorticosteronemia and a blunted increase of corticosterone after fasting compared with control animals. After fasting, FR30 animals showed no marked reduced POMC mRNA levels and -endorphin-immunoreactive fibers projections intensity. By contrast, NPY gene expression and immunoreactive fibers intensity increased. FR30 rats also displayed subtle food intake alterations. They exhibited higher body weight-related food intake, modified light/dark-phase rhythm and refeeding time-course after fasting. At rest, in the morning, they showed a hyperinsulinemia and a strikingly increase in the c-Fos-containing cells number in the arcuate nucleus. About 30% of the c-Fos-expressing cells were POMC neurons. Data suggested that maternal undernutrition differently programs the long-term offspring appetite regulatory system, specially the response of POMC neurons to energy status and food intake rhythm.