Impact of early postnatal overnutrition on cardiac mitochondrial dysfunction in adult mice with ischemia/reperfusion.

Background and aims: Nutritional imbalance at the beginning of life, a critical window period, leads to the development of obesity, overweight, dyslipidemia, diabetes, and cardiovascular disease in adulthood. In this study, the effects and associations of overnutrition during lactation on energy metabolism and oxidative stress in cardiomyocytes of adult male Swiss mice were examined.

Methods and results: Animals were divided into two groups (control and overfed) subjected to baseline and ischemia/reperfusion conditions, forming four groups: control baseline (CBL), control ischemia/reperfusion (CIR), overfed baseline (OBL), and overfed ischemia/reperfusion (OIR). The hearts were analyzed for hemodynamics using the Langendorff technique, mitochondrial energy metabolism using the Oroboros apparatus, ATP production, oxidative stress, and SIRT1, pSTAT3 and STAT3 protein content by Western blotting. Hemodynamic abnormalities in the cardiovascular system were associated with mitochondrial dysfunction, as demonstrated by impaired carbohydrate and fatty acid oxidation capacity, decreased mitochondrial coupling in the OG, and reduced ATP production in the OIR group. Alteration in pSTAT3 and SIRT1 proteins expression in overfed mice reinforce energy metabolism impairment. Lipid and/or protein degradation is altered in the heart of OG, suggesting increased oxidative stress.

Conclusion: Overnutrition during lactation associated with heart ischemia leads to molecular cardiac alterations in STAT3 and SIRT1 proteins, compromising energy metabolism via reduced mitochondrial oxidation capacity, ATP production and increased lipid peroxidation.