Abstract 16913: Maternal Obesity Impaired Mitochondrial Function of Term Fetal Heart in Sheep

Abstract

Introduction: Studies in human and animals suggest that maternal obesity (MO) negatively impacts fetal heart development and cardiac function. Epidemiological studies indicate MO could result in increased incidences of cardiovascular diseases in the offspring. However, the underlying mechanisms are still not well elucidated. Our group has developed and characterized a diet-based sheep model of MO beginning before pregnancy as is common in humans to study the effect of MO on fetal heart function. Previously, we have observed compromised contractility and intracellular calcium in MO fetal cardiomyocytes. Here, we look into the mitochondrial function of the term fetal myocardium. Hypothesis: MO impairs fetal heart mitochondrial function and ATP synthesis. Methods: From 60 days before and through pregnancy, ewes were fed either 100% of National Research Council (NRC) recommendations (control, n=6) or 150% of NRC’s recommendations (MO, n=7). At 135-day gestation (Term 150 days), the fetal heart was quickly removed under general anesthesia, and cardiomyocytes were isolated and mitochondria were prepared. Mitochondrial biogenesis was measured by using Seahorse extracellular flux analyzer (XF96) on isolated cardiomyocytes and mitochondrial oxidative phosphorylation complex activity were measured with Abcam assay kits. Analysis by Student’s t-test: *p < 0.05. Results: The Seahorse mitochondrial biogenesis data suggested that mitochondrial maximal and spare respiration rate were significantly reduced in MO fetal cardiomyocytes. More importantly, MO suppressed mitochondrial ATP production in MO fetal cardiomyocytes. The mitochondrial oxidative phosphorylation was downregulated in MO fetal myocardium. We found that complex I and IV enzyme activity was decreased in MO group. The activity of complex V, ATP synthase subunits, was reduced by 43% in MO fetal heart mitochondria. Conclusions: Our results suggest that MO induces stress uterus environment to fetal heart which impairs the mitochondrial function and ATP synthesis, which could be a possible mechanism of maternal obesity-induced cardiac contractile dysfunction.