0053 : Short-term moderate diet restriction in adulthood can reverse alterations of cardiac function induced by postnatal overfeeding in mice

Abstract

Postnatal overfeeding (OF) in rodents induces early programming of cardio-metabolic risk: permanent moderate increase in body weight, metabolic disorders and progressive alterations of cardiac function in adulthood. Our aim was to determine whether moderate diet restriction, performed at the time where these disorders are acquired, could restore cardiac function and ameliorate post-ischemic recovery. Immediately after birth, litters of C57BL/6 mice were either maintained at 9 (normal-fed group, NF), or reduced to 3 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 NF mice and OF mice were assigned to a moderate 20% calorie restriction (CR, NF-CR, OF-CR) for one month, while the other half of mice continued to eat AL (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 19.3% more than NF mice. Left ventricular fractional shortening (LVFS) and ejection fraction (LVEF, 51.4% vs. 57.6%, p<0.001) were decreased in OF mice. Left ventricular internal diameter in diastole (LVIDd) was significantly greater in OF mice. After one month of moderate CR, body weight of NF-CR and OF-CR was reduced by 12.6% as compared to their respective AL-group. LVEF increased in OF-CR (60.2% vs. 49.4%, p<0.001) and became comparable to this of NF-AL, while LVIDd was also normalized, whereas no difference between NF-CR and NFAL were observed. After 30min of global ischemia, hearts isolated from OFCR mice showed smaller infarct size than this of others groups. Our study suggests that while short-term moderate CR could diminish body weight in both NF and OF groups of mice, CR was able to improve cardiac function and susceptibility to myocardial ischemia-reperfusion injury only in OF, reversing the deleterious influence of postnatal programming by early overnutrition.