Abstract
Recent studies demonstrated that metabolic syndrome and cardiovascular diseases could be elicited by developmental programming, which is regulated by prenatal nutritional and environmental stress. In this study, we utilized a rat model to examine the effect of excessive maternal fructose intake during pregnancy and lactation on cardiac development and progression of pressure overload-induced cardiac hypertrophy in offspring. Transverse aortic constriction (TAC) was performed on 3-month-old male offspring to induce ventricular pressure overload. Four weeks post-TAC, echocardiographic assessment as well as histopathological and biochemical examinations were performed on the myocardium of the offspring. Echocardiographic and gross examinations showed that heart weight, interventricular septal thickness in diastole (IVD; d), and left ventricular posterior wall thickness in diastole (LVPW; d) were elevated in offspring with TAC and further increased by maternal fructose exposure (MFE). However, the left ventricular ejection function was not significantly affected. Myocardial histopathological examination revealed that the indices of fibrosis and oxidative stress were higher in offspring with MFE and TAC than those in animals receiving either treatment. Molecular examinations on the myocardium demonstrated an MFE-induced upregulation of p38-MAPK signaling. Next generation sequence (NGS) analysis indicated a modulation of the expression levels of several cardiac hypertrophy-associated genes, including GPR22, Myh7, Nppa, P2RX4, and Npy by MFE. Subsequent RT-PCR indicated that MFE regulated the expression levels of genes responsive to cardiac hypertrophy (i.e., Myh-7, ANP) and oxidative stress (i.e., GR, GPx, and NQO-1). In conclusion, MFE during pregnancy and lactation modulated myocardial gene expression, increased oxidative stress, and exacerbated ventricular pressure overload-induced cardiac remodeling in rat offspring.
Highlights
Thirty-two male offspring were categorized into four groups: Group NC, Group maternal fructose exposure (MFE), Group NC + transverse aortic constriction (TAC), group MFE + TAC
We first demonstrated that excessive excessive maternalintake of fructose during pregnancy and lactation resulted in mild myocardial hypertrophy (Table 1) and exacerbated cardiac remodeling post TAC-induced ventricular pressure overload (Figure 1)
The findings of this study demonstrate a regulatory role of MFE in cardiac myocardial gene expression and stress response to ventricular pressure overload, further investigations are needed to reveal the mechanistic interactions among maternal fructose intake, cardiac developmental programming, and response to myocardial stress in offspring
Summary
Previous studies have reported an adverse impact of the consumption of fructosecontaining beverages, which has significantly increased during past decades [1], on metabolism and body adiposity [2,3] such as caloric overconsumption, body weight gain, and induction of metabolic syndromes [2,4,5]. Environmental and nutritional insults in the developmental stage may lead to permanent changes in tissue structure and function in adulthood, a concept known as developmental programming [9]. Other reports have shown that permanent impacts on myocardial function, especially ventricular hypertrophy, may be attributed to maternal undernutrition [13]. Maternal nutrient restriction and overnutrition in sheep models revealed changes of gene expression profiles in the fetal left ventricle accompanied by cardiac hypertrophy and fibrosis [14,15,16]
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