Both undernutrition and overnutrition of the mother during pregnancy and lactation produce a syndrome of altered energy balance in the offspring and has long-lasting consequences on CNS systems regulating food intake, metabolism, and food reward. Homeostatic circulating factors like insulin, glucocorticoids, and leptin that are generally increased by exposure to high fat/high caloric diets constitute important signals in these processes. They trigger functional activation of specific intracellular cascades mediating cellular sensitivity, survival, and synaptic plasticity. Using a model whereby the late fetal and neonatal rat is exposed to increased high fat (HF) via HF feeding of the mother, we investigated the proximal (neonatal) and distal (adult) consequences on metabolism and hippocampal function in the offspring. Adult offspring of HF-fed mothers displayed several of the physiological and behavioral changes susceptible to leading to metabolic complications. These include elevated circulating concentrations of leptin and corticosterone, increased body weight gain and food intake, modest preference for fat-containing food types, as well as the onset of hypothalamic leptin resistance. In the hippocampus, HF-fed offspring or neonates treated with leptin show similar increases in neurogenesis and survival of newborn neurons. We identified some of the direct effects of leptin to increase synaptic proteins, N-methyl-d-aspartate (NMDA), and glucocorticoid receptors, and to reduce long-term potentiation (LTP) prior to weaning. While these studies have documented effects in animal models, concepts can easily be translated to human nutrition in order to help design better perinatal diets and nutritional preventive measures for mothers in a coordinated effort to curb the obesity trend.