Long-term impact of postnatal overfeeding on myocardial protective pathways

Abstract

Nutritional disturbances during the postnatal period may be responsible for a predisposition in adulthood to increased cardio-metabolic risk and a greater myocardial vulnerability to ischemia. This nutritional perinatal programming may also lead to an alteration of cellular pathways involved in cardiac protection, such as the specific RISK and SAFE pathways, highlighted during pre- and post-ischemic conditioning or those of sirtuins (SIRT), histone deacetylases involved in the regulation of essential biological process. Therefore, our goal was to evaluate the impact of postnatal overfeeding (PNOF) on myocardial expression of genes involved in heart protection against ischemia. PNOF was induced by reduction of litter size of C57/BL6 mice immediately after birth: normally-fed group (NF) was composed of 9 pups/mother and overfed group (OF) of 3 pups/mother. The gene expressions of proteins of interest composing the cardioprotective pathways (RISK pathway: Akt, ERK, SAFE pathway: JAK/STAT3, Sirtuins: SIRT1) were measured by RT-qPCR in mice aged 24 days, 4 and 6 month. PNOF induced an early and permanent increase in body weight in OF group. An early rise (at 24 days) of the gene expression of JAK, ERK1 and SIRT-1 was observed in OF group, whereas at 4 months the expression of these cardioprotective pathways was decreased, represented by a reduction in the gene expression of ERK1, Akt, JAK, STAT3 and SIRT1. To conclude, over time, in PNOF-treated mice, a decrease in the expression of signaling pathways involved in cardiac cellular protection occurs, which could explain why adult animals show increased susceptibility to cardiac ischemic lesions. The mechanism of this alteration of expression is not yet understood, but it could involve epigenetic modifications.