Abstract 887: Maternal Obesity “rafting” Offspring Toward Cardiovascular Disease: Palmitate Exposure In Utero Causes Systolic And Vascular Dysfunction Via Modified Lipid Raft Structure
Obesity has increased dramatically, and correlates with increased risk for cardiovascular disease (CD). However, it is unknown whether maternal obesity carries a risk for the developing fetus. Therefore, we tested whether maternal high palmitate feeding diminishes cardiac contractile performance in the offspring and determined changes in lipid rafts and eNOS activation, an indicator of vascular function. Wild type female mice (B6) were fed a high palmitate diet (P); (21% total fat of which 47% is P) or, as control, standard lab chow (S) 2 weeks prior to mating. After weaning each litter was split, half remaining on P and the other on S, leading to four groups investigated. To determine contractile performance (CP) in vivo, cardiac MR images were taken at 2, 4, and 12 weeks. Coronary flow was determined in the isovolumic Langendorff mode with varying extracellular [Ca2+] from 1.5 – 4 mM. Left ventricular (LV) total lipid extracts were used to measure ceramide (Cer) content by mass spectrometry. LV eNOS protein expression was determined by Western blotting. Heart weights and LV volumes indicated no hypertrophy in any group. P feeding resulted in a 5 – 6 fold increase of C18 Cer in cardiac membranes (Fig A⇓). In vivo, fractional shortening was decreased in all P-exposed pups (Fig B⇓). Moreover, coronary flow increased in P dam/P pup group 50 % at 2 wks and 24 % at 12 wks (Fig C⇓). This correlated with increased expression of eNOS, 192 % at 2 wks and 60% at 12 wks. Our results suggest that increased Cer content leads to systolic dysfunction and increased coronary flow due to eNOS upregulation. Thus, maternal P effects lipid rafts in the offspring and plays a key role in the pathogenesis of CD associated with obesity.