Abstract 14864: Parental Obesity Leads to Mild Diastolic Dysfunction and Impaired Exercise Tolerance, but Not Hypertension, in Female Offspring

Abstract

We found that parental obesity leads to high blood pressure (BP) and diastolic dysfunction in male offspring. Here, we examined the impact of parental obesity on BP regulation, systolic and diastolic function, and exercise tolerance in female offspring. The following groups were studied: 1) offspring fed normal diet (N) born from N lean parents (N-F1-N, n=5); 2) offspring fed high fat diet (H) born from N parents (N-F1-H, n=6); 3) offspring fed N born from H obese parents (H-F1-N, n=7); and 4) offspring fed H born from H obese parents (H-F1-H, n=7). Parents were fed H or N from weaning until the end of lactation, while offspring were placed on N or H diet from weaning until 22 weeks of age. Body weight, fat and lean mass were measured weekly (EchoMRI4-in-1 System). Cardiac function including ejection fraction (EF), isovolumetric relaxation time (IVRT), early (E’) and late (A’) mitral annular diastolic velocities were measured by echocardiography (VisualSonics VEVO-3100) using left ventricle long and short axes, pulse wave and tissue Doppler. BP, measured by telemetry, was similar among all groups. Compared to lean N-F1-N control mice, H-F1-N mice had similar body weight (23.7±0.1 vs. 25.2±1.8 g), fat mass (3.4±0.1 vs. 4.4±1.6 g) and lean mass (22.9±0.4 vs. 24.6±0.3 g). Both offspring groups fed H after weaning were heavier than offspring fed normal diet, however, H-F1-H mice were significantly heavier than N-F1-H mice (41.2±1.6 vs. 37.4±1.0 g) due to greater fat mass (16.2±1.1 vs. 13.2±1.0 g) and lean mass (25.1±1.7 vs. 22.9 vs. 0.3 g). Despite no major differences in EF among all 4 groups, mice born from obese H parents exhibited signs of diastolic dysfunction, irrespective of their own diet, as indicated by reduced E’/A’ ratio (0.8±0.1 and 1.2±0.2 vs. 1.6±0.1 and 1.5±0.2, for H-F1-H and H-F1-N vs. N-F1-N and H-F1-H, respectively), reduced exercise capacity (4.2±0.7 and 4.7±0.5 vs. 5.9±0.7 and 7.4±0.3 m.kg), and increased IVRT in obese H-F1-H compared to obese N-F1-H (28.4±2.3 vs. 22.2±0.8 ms). These results indicate that despite no alterations in BP diet-induced parental obesity is associated with signs of diastolic dysfunction and impaired fitness in female offspring, which is exacerbated by continuing to feed the offspring with H diet.