There is growing evidence that early nutrition has a major impact on susceptibility to obesity. To determine the basis for energy balance programming we have established a rat model of altered early life nutrition with control animals (offspring of control dams fed a 20% protein diet), recuperated animals who experienced poor fetal growth then catch-up growth (offspring of dams fed an isocaloric low-protein (8%) diet during pregnancy, but nursed by control dams fed a 20% protein diet) and postnatal low-protein animals who grew slowly during lactation (offspring of control dams (20% protein) diet nursed by low-protein (8%) diet fed dams)[1]. The impact of this early life nutritional manipulation on the energy balance system was evaluated by measuring hormone concentrations along with anatomically specific hypothalamic expression of genes measured by in situ hybridisation [2,3]. Two male pups were collected from each litter (giving n=8) at weaning. Data is shown as mean ± SEM unless otherwise stated and was analysed using one-way ANOVA. Recuperated pups were smaller at birth (6.6 ± 0.2g vs. 7.5 ± 0.2g, p<0.001), but caught up with controls by day 14 (34.9 ± 0.7g vs. 33.4 ± 1.0g). At weaning, despite similar body and fat pat weights, recuperated offspring were hypoleptinemic in the fed state compared to controls (1.9 ± 0.3 ng/ml vs. 4.4 ± 0.4 ng/ml, p<0.001). Postnatal low-protein offspring had lower body weights than control offspring (25.0 ± 1.2g vs. 54.6 ± 1.0g, p<0.001), and were hypoglycemic (6.2 ± 0.8 mM vs. 9.1 ± 0.6 mM, p<0.05) hypoinsulinemic (4 [3-5] pM vs. 96 [74-132] pM, p<0.001, data shown as geometric mean and 95% confidence intervals) and hypoleptinemic (1.5 ± 0.3 ng/ml vs. 4.4 ± 0.4 ng/ml, p<0.001) at weaning. Leptin receptor gene expression in the arcuate nucleus (ARC) was increased in postnatal low-protein offspring compared to controls (310 ± 54% vs. 100 ± 8%, p<0.05) and expression of the suppressor of cytokine signaling-3 (42 ± 14% vs. 100 ± 11%, p<0.001) was decreased. Consistent with reduced serum leptin in postnatal low-protein offspring, ARC gene expression for orexigenic neuropeptides, neuropeptide Y (151 ± 8% vs. 100 ± 6%, p<0.001) and, agouti-related peptide (201 ± 14% vs. 100 ± 5%, p<0.001) was increased, and that for anorexigenic neuropeptides, proopiomelanocortin (41 ± 8% vs. 100 ± 4%, p<0.001) and cocaine-and amphetamine-regulated transcript (26 ± 3% vs. 100 ± 4%, p<0.001) was decreased. This increase in anabolic drive could indicate that central pathways recognise the energy deficit, but fail to redress the imbalance. These results suggest that the early nutritional environment can affect the development of energy balance circuits and consequently alter future obesity risk.