0229: Alterations of cardiac function induced by postnatal overfeeding can be reversed by moderate diet restriction

Abstract

Postnatal overfeeding (OF) in rodents induces a permanent moderate increase in body weight, metabolic disorders and progressive alterations of cardiac function. Our aim was to determine whether moderate diet restriction could restore cardiac function in mature overfed mice. Immediately after birth, litters of C57BL/6 mice were either maintained at nine (normal-fed group, NF), or reduced to three in order to induce OF. At weaning, mice of both groups received a standard diet ad libitum (AL) . At 6 months of age, half of the OF mice were assigned to a moderate 20% calorie restriction (CR, OF- CR ) for one month, while NF and the other half of the OF mice continued to eat ad libitum (NF-AL , OF- AL) . Cardiac function was followed using echocardiography and, at 7 months, the sensitivity to ischemia-reperfusion injury was evaluated in isolated perfused hearts. Six-month-old OF mice weighed 22.5% more than NF mice. Left ventricular fractional shortening (LVFS) and ejection fraction (LVEF) were decreased in OF mice (25.5% vs. 30.5% for LVFS; 50% vs. 58% for LVEF, P<0.05). Left ventricular internal diameter in diastole (LVIDd) and systole (LVIDs) were significantly greater in OF than NF mice. One month of moderate CR normalized body weight in OF-CR compared with OF-AL (31.1 vs. 37.4 g, p<0.001). Moreover, LVEF was greater in OF- CR than OF-AL (61% vs. 52%, p<0.05) and became comparable to that in NF-AL. LVIDd and LVIDs were also normalized in OF- CR . Ex vivo, after 30 min of global ischemia, hearts isolated from OF CR mice showed better functional recovery than those of the two other groups. Our study suggests that short-term moderate diet restriction could normalize body weight gain induced by postnatal OF and, interestingly, could reverse alterations of cardiac function and susceptibility to myocardial ischemia-reperfusion injury in OF.