Exacerbated cardiac dysfunction after myocardial infarction in offspring from obese parents

Abstract

The prevalence of obesity in women of reproductive age is increasing rapidly, and children from obese mothers are at higher risk of developing cardiovascular diseases in adulthood. Acute myocardial infarction (MI) is one of the leading causes of death worldwide with more than one million deaths per year in the U.S. alone. Using a model of parental obesity with male and female Sprague-Dawley rats fed a high fat diet (HFD) prior to mating, and dams maintained on the HFD during gestation and lactation, we found that male and female offspring from these obese parents have multiple metabolic abnormalities early in life (3 weeks old), and that male, but not female, offspring have impaired diastolic function associated with reduced cardiac SIRT3 expression and mitochondrial biogenesis. At 24 weeks of age, male offspring from obese parents exhibit increased blood pressure. To examine if offspring from obese parents are at greater risk of death and worse cardiac function after MI, male and female lean offspring fed a normal diet (ND) born from ND fed lean parents (ND-Offs, n=5-6/sex) and lean offspring fed ND born from HFD fed obese parents (HFD-Offs, n=6-11/sex) were submitted to a permanent left descending coronary artery ligation to induce MI at 12 weeks of age. Twenty-four-hour survival rate post-MI surgery was examined and cardiac function was measured by intraventricular catheterization with a Millar catheter on day 7 post-MI. Compared to ND-Offs, male and female HFD-Off born from obese HFD-fed parents exhibited reduced survival rate (male: 60% vs 100% and female: 55% vs. 83% for HFD-Offs and ND-Offs, respectively) and increased ventricular fibrillation post-MI. At day 7 post-MI, we observed reduced +dP/dtmax in male, but not female, HFD-Offs compared to ND-Offs (6,554±25 vs. 8,253±440 mmHg/sec in males and 7,962±557 vs. 7,668±890 mmHg/sec in females, for HFD-Offs and ND-Offs, respectively) despite similar infarct size in all groups (~40% of the total left ventricle circumference). We found no major differences in -dP/dtmin or tau (indices of diastolic function) between groups. Thus, parental obesity is associated with increased mortality rate in their offspring after induction of MI and worse systolic function in male, but not female, offspring even when offspring are fed a healthy diet after weaning and remain lean. NIDDK 1R01121411 (do Carmo), HL1630376 (da Silva/do Carmo), NIGMS P20GM104357 (Hall), P30GM149404 (Hall) and U54GM115428 (Hall). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.