Obesity is a major health concern worldwide. Many therapies have been developed in an attempt to combat its increasing prevalence. High fat diet and stress have been shown to play a major role in the development of obesity. The effect of high fat diet in the brain and its downstream effect throughout the body is not completely understood. The inflammation in the central nervous system that occurs after high fat feeding has the potential to disrupt metabolic homeostasis and neurotransmission in the brain. Anti-inflammatory drugs are readily available on the market and may be an easy therapy to treat the neuroinflammation that results from consumption of a high fat di-et. Our study found that an anti-inflammatory drug does in fact suppress microglia activation, therefore decreasing brain inflammation. In addition to the simple consumption of high fat diet, stress is a compounding factor that plays a major role in the development of obesity. Fetal programming is a concept that is now being used in many studies in an attempt to understand the factors that might predispose offspring to developing diseases like obesity in adulthood. Prenatal stress followed by postnatal high fat diet exposure may be a very effective paradigm to study the mechanisms involved that promote obesity in the offspring. A diet induced obese animal model that is genetically predisposed to obesity along with its lean counterpart was used in these studies. This model was used to study the complex interaction between genes, prenatal stress, high fat diet, and sex in the development of obesity. Our study found that maternal stress did in fact pro-gram the offspring to develop obesity and modulate other metabolic factors after being challenged with high fat diet. The impact of these interactions on neurotransmitter systems and hormones is presented and our study shows significant differences between the genetic, prenatal stress, diet, and sex groups. Preliminary understanding of brain neurotransmission in this context might help us to draw a more complete picture of the changes associated with a high fat diet-induced inflammatory state.