Abstract 090: Intergenerational Inheritance of Obesity-Induced Diastolic Dysfunction With Preserved Ejection Fraction

Abstract

Obesity is strongly associated with cardiomyopathy and heart failure. We examined the impact of paternal and maternal obesity on systolic and diastolic function in male adult offspring. The following groups were studied: 1) offspring fed normal diet (ND) born from ND parents (ND-F1-ND, n=5); 2) offspring fed high fat diet (HFD) born from ND parents (HFD-F1-ND, n=6); 3) offspring fed ND born from HFD parents (ND-F1-HFD, n=7); and 4) offspring fed HFD born from HFD parents (HFD-F1-HFD, n=7). Parents were fed HFD or ND from weaning until the end of lactation, while the offspring were placed on ND or HFD from weaning until the end of experiments. Body weight, fat and lean mass, measured using EchoMRI4-in-1 System, were measured weekly. Cardiac function including ejection fraction (EF), isovolumetric relaxation time (IVRT), late filling velocity (A’), E and E’ early filling velocities were determined at 22 weeks of age using long and short axis left ventricle dimensions, pulse wave and tissue Doppler (VisualSonics 30 MHZ transducer, VEVO3100®). Compared to lean control ND-F1-ND mice, ND-F1-HFD mice had similar body weight (28.9±1.0 vs. 27.9±0.4 g) but higher fat mass (4.5±0.9 vs. 3.0±0.3 g) and lower lean mass (22.9±0.4 vs. 24.6±0.3 g). Both groups of mice fed HFD after weaning were heavier than offspring fed ND. However, HFD-F1-HFD mice were heavier than HFD-F1-ND mice (47.3±0.8 vs. 42.5±1.9 g) due to greater fat mass (19.4±0.6 vs. 15.7±1.6 g) and lean mass (28.3±0.6 vs. 26.9 vs. 0.3 g). Despite no major differences in ejection fraction among all 4 groups, mice fed HFD or born from parents fed HFD exhibited diastolic dysfunction; worse indicators of diastolic function were observed in mice from HFD parents as indicated by increased IVRT (30.4±1.8, 25.0±1.8, 22.1±2.0 vs. 21.4±0.9 ms) and E/E’ ratio (36.6±3.6, 32.3±1.8, 31.8±1.2 vs. 27.9±2.5) and reduced E’/A’ ratio (0.9±0.1, 0.7±0.1, 1.5±0.2 vs. 1.4±0.1) for HFD-F1-HFD, ND-F1-HFD, HFD-F1-ND and ND-F1-ND, respectively. These results indicate that diet-induced parental obesity is associated with diastolic dysfunction and preserved EF in the offspring, which is exacerbated by HFD-induced obesity. (NHLBI-PO1HL51971, NIGMS P20GM104357 and U54GM115428)