PURPOSE Gestational exposure to maternal obesity increases the risk of cardiovascular disease in the offspring. Exposure to overnutrition during fetal life is likely to be followed by continued exposure to the same calorie-rich environment post-natally. The aim of this project was to characterize the consequences of combined exposure to a maternal and post-natal obesogenic diet on offspring cardiac structure and function.
METHODS A well-established mouse model of maternal diet-induced obesity where C57bl/6 dams are fed a high fat/high simple carbohydrate diet during pre-gestation, gestation and lactation was used. Male offspring from control (C-) and obese (O-) were assigned at weaning to either a control (-C) or obesogenic diet (-O), generating 4 experimental groups (CC, CO, OC and OO). Metabolic profile, cardiac structure and function, gene expression, and blood pressure were assessed in male offspring at 8 weeks of age. RESULTS Dams fed the obesogenic diet were significantly heavier on the day of mating (p<0.0001), and remained heavier throughout pregnancy and at weaning compared to controls. Young adult (8 weeks) offspring exposed to maternal overnutrition had heavier hearts (17%) than control mice (effect of maternal diet p=0.005). A post-weaning obesogenic diet also increased heart weight (effect of offspring diet p=0.019). Circulating levels of insulin and leptin were increased by feeding the obesogenic diet, and further elevated by the maternal exposure. Mice born to overnourished mothers developed pathological ventricular remodelling associated with re-expression of cardiac fetal genes (Nppa, Myh7, Myh7:Myh6 ratio), interventricular septum thickening (p=0.0004), increased left ventricular area (p=0.02), cardiac systolic dysfunction with reduced ejection fraction and fractional shortening. Most importantly, up-regulation of genes involved in cardiac contraction was observed in fetuses from obese dams as early as in utero. CONCLUSIONS Maternal overnutrition programs adverse cardiac remodelling and dysfunction in adult male offspring. These findings suggest that a maternal caloric-rich uterine environment is a critical determinant of cardiovascular disease risk in the next generation, and is as detrimental as current obesity.