Nutritional factors have a critical influence during prenatal life on the development and regulation of networks involved in body weight and feeding regulation. To establish the influence of the macronutrient type on feeding regulatory mechanisms and more particularly on stimulatory pathways (galanin and orexins), we fed female rats on either a high-carbohydrate (HC), a high-fat (HF), or a well-balanced control diet during gestation and lactation, and measured peptide expression in the hypothalamus and important hormones (leptin, insulin) in their pups at weaning. HF weanlings were 30% lighter than control and HC pups (P < 0.001). They were characterized by reduced plasma glucose and insulin levels (P < 0.01 or less). Their galanin and orexin systems were upregulated as shown by the significant augmentation of mRNA expression in the paraventricular nucleus and lateral hypothalamus, respectively. Inhibitory peptides like corticotropin-releasing hormone and neurotensin were not affected by this dietary treatment during early life. There was, therefore, a more intense drive to eat in HF pups, perhaps to compensate for the lower body weight at weaning. HF diets during early life had meanwhile some positive consequences: the lower metabolic profile might be beneficial in precluding the development of obesity and metabolic syndrome later in life. This is however valid only if the orexigenic drive is normalized after weaning. (c) 2006 Elsevier Inc. All rights reserved.