Abstract 217: Cardiac Dysfunction in Offspring of Obese Multiparous Females

Abstract

Emerging evidence indicates that maternal events prior to birth have a powerful impact on the risk for age-related diseases. Indeed, mothers who are obese during pregnancy confer an increased risk on their offspring for developmental programming of metabolic diseases. An often-overlooked risk factor for female obesity, and thus developmental programming, is multiparity. We have developed a novel mouse model in which multiparous mice become obese and develop severe inflammation − mirroring the pathology of obese multiparous humans. We have previously reported that the adult offspring of multiparous mice exhibit increased adiposity and a reduction in expression levels of genes associated with energy expenditure when fed low fat diets, despite similar food consumption. Recent studies show that these defects are associated with reduced energy expenditure and reduced mitochondrial function in hepatocytes of these mice compared to adult offspring of primiparous mice. Since a change in mitochondrial function in cardiomyocytes can lead to abnormal heart function, we fed male offspring a high fat diet (41% calories; milk fat) to stress the metabolic system. All mice accrued the same amount of fat on the high fat diets. We then and measured cardiac function using an echocardiogram. We found that there were significant differences in the ejection time, left ventricle mass, fractional shortening, and importantly in stroke volume and cardiac output of male offspring from females in their 1 st vs 4 th (multiparous) pregnancy. No differences in heart rate and aorta diameter were observed. These data suggest that the offspring of obese multiparous females are more prone to develop reduced cardiac function on a high fat diet, possibly indicating that maternal environment may be a novel risk factor for heart disease.