Parental obesity predisposes male and female offspring to exacerbated cardiac dysfunction and increased mortality after myocardial infarction

Acute myocardial infarction (MI) is a leading cause of death worldwide, accounting for >1 million deaths/year in the United States alone. Although parental obesity is a risk factor for offspring cardiovascular diseases, the impact of parental obesity on offspring outcomes after MI is unknown. This study examined if non-obese male and female offspring from obese Sprague-Dawley rat parents fed a high-fat diet (HFD-Offs, <i>n</i> = 11-19/sex) are at greater risk of death and worse cardiac dysfunction after MI, compared with offspring from lean parents fed a normal diet (ND-Offs, <i>n</i> = 12-15/sex). All offspring were fed ND from weaning and subjected to left descending coronary artery ligation at 12 wk of age to induce MI. Survival rate 24 h post-MI was examined, and cardiac function was measured by echocardiography and intraventricular catheterization with a Millar catheter on <i>day 7</i> post-MI. Compared with ND-Offs, male and female HFD-Offs exhibited increased ventricular fibrillation and reduced survival post-MI (male: 37% vs. 80% and female: 55% vs. 83% for HFD-Offs and ND-Offs, respectively). In surviving rats, systolic dysfunction was more pronounced in male and female HFD-Offs compared with ND-Offs at <i>day 7</i> post-MI, despite similar infarct size in all groups. We also found reductions in baseline O₂ consumption rate and pyruvate-supported mitochondrial respiration, as well as increased mitochondria-derived superoxide production in cardiac fibers from HFD-Offs. Thus, parental obesity is associated with an increased 24-h mortality rate in their offspring after induction of MI and worse systolic function even when the offspring are fed a healthy diet after weaning and remain lean.<b>NEW & NOTEWORTHY</b> A major new finding of this study is that parental obesity markedly reduces survival rate and exacerbates cardiac dysfunction after myocardial infarction in their offspring, and this effect is independent of offspring sex.