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

Abstract

Acute myocardial infarction (MI) is a leading cause of death worldwide, accounting for >1 million deaths/year in the U.S. 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 high fat diet (HFD-Offs, n=11-19/sex) are at greater risk of death and worse cardiac dysfunction after MI, compared to offspring from lean parents fed normal diet (ND-Offs, n=12-15/sex). All offspring were fed ND from weaning, and subjected to left descending coronary artery ligation at 12 weeks of age to induce MI. Survival rate 24 hrs post-MI was examined and cardiac function was measured by echocardiography and intraventricular catheterization with a Millar catheter on day 7 post-MI. Compared to ND-Offs, male and female HFD-Off 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 to ND-Offs at day 7 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 increased 24-hour 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.