Influence of postnatal overfeeding on postnatal heart development in juvenile mice

Shortly after birth, cardiomyocytes progressively lose their ability to proliferate to switch towards a hypertrophic growth and this ability is known to be influenced by nutritional factors. Postnatal overfeeding (PNOF) induced by litter size reduction in rodents reproduces the impact of childhood overnutrition and was shown to alter levels of circulating metabolites (lipids and glucose). Moreover, PNOF is known to have a major impact on metabolic status and cardiac function in adulthood. The aim of this work was to study the impact of PNOF on postnatal cardiac proliferation and apoptosis in juvenile mice. C57BL/6 male pups were raised in litter adjusted either to 9 or 3 pups for control (NF) and PNOF group respectively. At 7, 10 or 24 days after birth, hearts were harvested for immunostaining of proliferation marker Ki67 or apoptosis marker caspase 3. Cardiomyocyte number was also counted in hearts of 24 days-old mice and RT-qPCR were performed to study different cyclin mRNA expressions. At 7, 10 and 24 days, body weight and heart mass of PNOF mice was significantly higher than control mice. The proliferation rate of cardiomyocytes in PNOF hearts was decreased at 7 and 10 days with no signs of apoptosis at 7 days. At 24 days-old, even though the proliferation rate was not different between the two groups, the number of cardiomyocytes per mg of tissue was smaller in PNOF hearts and associated to a decreased expression of cyclins D1 and A2. In this study we observed that PNOF does impact the postnatal proliferative window of cardiomyocytes by reducing their proliferation rate 7 and 10 days after birth. This leads to a diminution of cardiomyocytes number in PNOF hearts at weaning and is associated to a decreased expression of specific cyclins essential for the cell cycle progression. Such a decrease could later be involved in the long-term cardiac alterations observed in PNOF mice.