Abstract 13098: Maternal Obesity and Insulin Resistance Lead to Endothelial and Myocardial Mircovascular Dysfunction in Nonhuman Primate Offspring
Background: There is a well-defined link between maternal under-nutrition and cardiovascular disease late in life. However, little is known about maternal over-nutrition and cardiovascular health in the early postnatal period. We hypothesized that exposure to a high fat diet (HFD) during gestation and the postnatal period would lead to vascular dysfunction in non-human primate offspring.
Methods: Forty-four infant Japanese macaques were exposed to either a control diet (CTR) or a HFD during gestation and the postnatal period. Initial infant studies were performed prior to weaning at 5 months. Infants were either continued on the same diet (CTR/CTR or HFD/HFD) or switched diets post weaning (CTR/HFD, HFD/CTR) and restudied at 1 yr. The following tests were performed at each time point: intravenous glucose tolerance test to assess the degree of insulin resistance (IR), dual x-ray absorptiometry for fat quantification, brachial artery flow mediated vasodilation (FMD) for endothelial function, and rest/stress contrast echocardiography for myocardial blood flow.
Results: Mothers on HFD were obese and IR compared to age matched controls. At 5 mos, infants exposed to a HFD were overweight and IR with a 40% increase in both truncal fat (p=0.09) and insulin area-under-the curve concentration (p < 0.03) compared to CTR infants. In addition, FMD was reduced by 70% (p< 0.01) and peak myocardial blood flux rate was reduced by 26% (p < 0.04) compared to CTR. The degree of IR correlated with reductions in FMD (R = -0.57, p<0.001) and reductions in the peak myocardial blood flux rate (R = -0.29, p<0.04). Continuous exposure to a HFD resulted in a persistent 64% reduction in FMD (p< 0.01) at 1yr. FMD improved by 86% after dietary change (HFD/HFD 1.5±0.2% vs HFD/CTR 2.8±0.6%, p < 0.04) although it did not fully restore endothelial function (CTR/CTR 4.1±1.0%). The early differences in myocardial blood flow at 5 mos were not observed at 1 yr.
Conclusions: Gestational and postnatal exposure to a HFD results in obesity, IR, endothelial dysfunction, and myocardial microvascular dysfunction in early life. Improved infant nutrition can mitigate but not fully reverse endothelial dysfunction. Consequently, both maternal and infant nutrition are important for early cardiovascular health.
- © 2013 by American Heart Association, Inc.