Project summary: Cardiovascular disease (CVD) is the leading cause of death in the United States. CVD develops as a result of genetic or lifestyle components, and it has now been established that CVD can also originate as a consequence of insults to the maternal environment during critical windows of prenatal development. In fact, studies have shown that maternal obesity or a high fat diet during pregnancy is associated with elevated risk for the development of cardiovascular diseases (such as hypertrophy, reduced contractile function and hypertension) in adult offspring. Regular exercise is an important therapeutic treatment used in patients to prevent the onset of cardiovascular and metabolic diseases. Studies in our lab and others have shown that in a rodent model, maternal exercise improves the metabolic health of adult offspring from chow-fed dams and negates the detrimental effects of maternal high-fat diet on offspring metabolic health. However, the effects of maternal exercise on the cardiac health of adult offspring have not been well investigated. Our exciting preliminary data demonstrate that adult offspring from exercised dams have preserved cardiac function compared to offspring from sedentary mothers; while offspring from HFD-fed sedentary dams have impaired cardiac function. Importantly, maternal exercise negates the detrimental effects of a maternal high-fat diet on adult offspring cardiac function. The proposed study will determine the ability of maternal exercise to prevent the detrimental effects of a maternal HFD, and be the first to identify the efficacy of maternal exercise to preserve cardiac function in male and female offspring from chow-fed dams. Importantly, these studies will identify the mechanism(s) through which maternal exercise exerts beneficial effects on offspring cardiac health. We will do this using two specific aims: Aim 1 will determine the effects of maternal exercise on offspring cardiomyocyte contractile function, calcium handling, and respiration, and Aim 2 will determine the genetic and/or epigenetic mechanism(s) behind these effects. By determining the mechanism behind maternal exercise induced protections on offspring cardiac health, this proposal will potentially provide identify novel therapeutic targets to protect against the development of cardiac disease.