Grant: Project Grant

Babies born to mothers who were obese or diabetic during pregnancy are more likely to develop risk factors for cardiovascular disease before they reach adulthood. Given that these metabolic disorders have become the most common complications of pregnancy, they have likely contributed significantly to the current epidemic of early-onset cardiovascular risk among Canadian youth. We have developed novel mouse models of maternal metabolic dysfunction that allow us to identify the developmental perturbations underlying later-life risk and understand how these perturbations impact health at the level of the cell, organ and organ system. Our data suggest that early-onset cardiovascular risk results from a perturbation in the development of fat tissue during fetal life that impairs its ability to expand after birth. Expansion of fat tissue to buffer excess energy plays a critical role in maintaining cardiovascular health under conditions of high caloric intake. Fat tissue has a defined limit of expansion, which is eventually reached as an individual gains weight. Recent studies in obese humans reveal that a failure in fat tissue expansion precipitates the onset of obesity-associated cardiovascular disease. Therefore, we will test the hypothesis that early-onset cardiovascular risk in offspring born to mothers with metabolic dysfunction during pregnancy results from accelerated fat cell maturation leading to a premature limitation in fat expansion. Polyunsaturated fatty acids (PUFA) promote cardiovascular health by regulating fat cell expansion. Several clinical trials have demonstrated PUFA supplementation to be safe in human infants; however, their utility in optimizing long-term cardiovascular health in infants born to obese or diabetic mothers is currently unknown. Thus, we will determine if early-life PUFA supplementation prevents the development of cardiovascular risk factors in babies born to pregnancies complicated by maternal metabolic dysfunction.