Hemodinâmica e metabolismo energético mitocondrial no coração de camundongos adultos obesos programados por hipernutrição na lactação

Abstract

The nutritional imbalance at the beginning of life in the period known as critical window, leads to the development of obesity, dyslipidemia, diabetes and cardiovascular disease in adulthood. This study aimed to analyze in male Swiss mice adults at 120 days of life the effects and associations of overnutrition on lactation by reducing litter on hemodynamic parameters, in mitochondrial energy metabolism (respiratory control ratio and oxidation of carbohydrates and fatty acids), in ATP production, in cardiac, hepatic and plasma oxidative stress, in molecular biology by key proteins and collagen deposition in heart. The mice were divided into two groups (control and overfed) subject to two conditions (baseline and ischemia/reperfusion) forming four groups in total: control group baseline (CGBL), control group ischemia/reperfusion (CGIR), overfed group baseline (OGBL) and overfed group ischemia/reperfusion (OGIR). The OG developed increased weight of the left ventricle, central fat and fasting glucose. Plasma levels of insulin and leptin are increased in OG compared to the CG. EDP, Max dP/dt and Min dP/dt parameters showed significant differences in baseline and post-ischemic presenting OGIR an increase of EDP and Min dP/dt and reduce of Max dP / dt compared to OGBL and increase of EDP compared to CGIR. Imbalances in cardiac hemodynamics were associated with mitochondrial dysfunction as observed by the reduction on fatty acid and carbohydrate oxidation and in the RCR to carbohydrate in OG and the reduction in ATP production in OGIR compared to CGIR and OGBL. Furthermore, cardiac hypertrophy markers as ANP is increase in OGIR and BNP in OGBL, increased collagen deposition in OGIR compared to OGBL and GCIR as well as in CGIR compared with CGBL, increased post-ischemia sensitivity in insulin signaling pathway with increased of PTP1B, IRS1 and pAKT2 and reduced pAKT1, AKT2, AMPK, pAMPK and reduced capacity utilization of fatty acids by reducing the content of CD36 and FABP. Finally, it was showed that the degradation of lipids and/or proteins is altered between CG and OG in heart, liver and plasma. The study demonstrates significant consequences of overnutrition on lactation by reducing litter on cardiac hemodynamic, cardiac sensitivity to ischemia and cardiac remodeling due to readjustments on cardiac energy metabolism via changes in insulin signaling pathway, reduction in ATP production and oxidation of energy substrates.