Abstract
BackgroundPostnatal overfeeding (OF) in rodents induces a permanent moderate increase in body weight in adulthood. However, the repercussions of postnatal OF on cardiac gene expression, cardiac metabolism and nitro-oxidative stress are less well known.Methodology/Principal FindingsImmediately after birth, litters of C57BL/6 mice were either maintained at 10 (normal-fed group, NF), or reduced to 3 in order to induce OF. At weaning, mice of both groups received a standard diet. The cardiac gene expression profile was determined at weaning and cardiac metabolism and oxidative stress were assessed at 7 months. The cardiac expression of several genes, including members of the extracellular matrix and apelin pathway, was modified in juvenile OF mice. In adult mice, OF led to an increase in body weight (+30%) and to significant increases in plasma cholesterol, insulin and leptin levels. Myocardial oxidative stress, SOD and catalase activity and mRNA expression were increased in OF mice. In vivo, diastolic and systolic blood pressures were significantly higher and LV shortening and ejection fraction were decreased in OF mice. Ex vivo, after 30 min of ischemia, hearts isolated from OF mice showed lower functional recovery and larger infarct size (31% vs. 54%, p<0.05). Increases in collagen deposition and expression/activity of matrix-metalloproteinase-2 were observed in adult OF mouse hearts. Moreover, an increase in the expression of SOCS-3 and a decrease in STAT-3 phosphorylation were observed in ventricular tissues from OF mice.Conclusions/SignificanceOur study emphasizes that over-nutrition during the immediate postnatal period in mice leads to early changes in cardiac gene expression, which may permanently modify the heart’s structural organization and metabolism and could contribute to a greater susceptibility to myocardial ischemia-reperfusion injury.
Highlights
Clinical and experimental evidence indicates that the environment during the peri-natal period and early development plays a key role in regulating metabolic tendencies in adulthood, and that nutrition in early life has an impact on the subsequent risk of overweight, hypertension and insulin resistance
Our results show for the first time that the nutritional environment during the postnatal period induces early changes in heart gene expression that may have a long-term effect on cardiovascular function and heart structure in adult mice; and may have a deleterious impact on myocardial injury recovery after an ischemic insult
Our study provides new original data and bring to light the fact that nutritional conditions in immediate postnatal life, such as overnutrition, may influence the expression of several genes involved in the heart’s structural organization metabolism and somatotropic system, vasoreactivity, ion channels (Scn4b), cell signaling/communication (APJ) and oxidative stress
Summary
Clinical and experimental evidence indicates that the environment during the peri-natal period and early development plays a key role in regulating metabolic tendencies in adulthood, and that nutrition in early life has an impact on the subsequent risk of overweight, hypertension and insulin resistance. Due to plasticity in gene expression, the neonatal period is critical for the orientation of phenotypic features in adulthood, since epigenetic modifications may permanently impact gene expression and influence the development of chronic diseases. In this field, several groups have shown that inducing early post-natal over-nutrition in rats, just by reducing litter sizes, led to substantial changes in body weight at weaning (nearly 30% increase), which persisted at a lower level in mature animals (10–15% increase) [1,2,3]. The repercussions of postnatal OF on cardiac gene expression, cardiac metabolism and nitro-oxidative stress are less well known
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