Obesity is one of the leading drivers of healthcare costs associated with preventable chronic disease. On average, U.S. adults gain on average 0.4 to 1 kg per year and it is likely that much of this annual weight gain is an additive result of short-term dietary excess. A significant factor driving short-term weight gain is overconsumption of foods high in fat. Even prior to weight gain, high dietary fat consumption can induce metabolic and physiological changes that are predictive of future weight gain and disease. Animal models used to study the effects of dietary manipulations have paid particular attention to the impact of diet on the brain; however the impact of acute fat intake on the brain has been less well studied. The following chapters provide a rationale for studying the impact of high fat diet on the hippocampus, a brain structure important for learning and memory, and supply novel evidence that acute high fat diet consumption alters hippocampal gene transcription as well as behavior in rats. Finally, we show that exposure to a high fat diet prior to weaning impacts the hippocampal gene expression in mouse offspring in a sex- and time-specific manner.