Vels were increased in the heart in response to both early overnutrition and I/R (P,0.01 and P,0.001 respectively, Figure 6B), with the levels of this anti-apoptotic protein being greater in overfed-IR rats than in control-IR (P,0.01).Inflammatory Markers in the MyocardiumiNOS content in the heart was unchanged in response to both early overfeeding and I/R. COX-2 levels were increased in the heart of overfed rats compared to controls (P,0.001, Figure 7A). I/R did not modify COX-2 levels in the heart of control rats but it decreased the levels of this protein in the heart of overfed rats (P,0.01, Figure 6B).DiscussionIn this study, we have used an experimental model of early overnutrition in rats by litter reduction in order to assess the effects of early overweight on cardiac function. As previously described, litter reduction increased food intake, and resulted in a higher weight gain and fat mass compared with control litters [28], [21,29,30]. This correlated with higher plasma levels of leptin in overfed rats. 
These alterations may be due, at least in part, to impaired response of neurons in arcuate and ventromedial hypothalamic nuclei to the anorexigenic effects of leptin andinsulin [23,31]as well as to altered metabolic activity of adipose tissue [32]. Previous studies had reported cardiovascular alterations in early overfed rats such an increase in blood pressure [32]and cardiac fibrosis [8]. However, to our knowledge this is the first study showing the deleterious effects of early overnutrition on cardiac function. These alterations could be due, at least in part, to changes in cardiomyocytes maturation as it is reported that this process in the rat takes place during late prenatal or early postnatal life [33]. In addition different perinatal insults, such as poor nutrition, hypoxia and endocrine stress are reported to alter this process inducing an alteration of the number of cells in the myocardium [34]. The perfused AKT inhibitor 2 hearts from overfed rats showed reduced left ventricular developed pressure, which may be due to impaired myocardial contractility in those hearts. This myocardial impairment was accompanied by increased expression of apoptosis markers in the hearts of overfed rats. However it is interesting that antiapoptotic markers were also increased in this condition, which may constitute an attempt of compensation by myocardial cells. Expression of COX-2 was also increased in the hearts of early overfed rats. This enzyme isoform is induced in 15755315 inflammatory states, and therefore may be considered an inflammation marker. This apoptotic and inflammatory condition in hearts of overfed rats may damage myocardial cells and result in reduced contractility. In obese patients, increased cardiac output and systolic volume is usually observed, and this increase may be related to the higher blood flow needed as a result of higher body mass. However, when the difference in body weight is taken into 117793 chemical information account, obese subjects present reduced cardiac index and reduced myocardial contractility [35,36]. These alterations could be due to increased production of free radicals, inflammatory mediators and apoptotic markers in the heart [37]. Indeed, in the heart of Zucker obese rats, an increase in the levels of apoptotic markers such asEffects of Ischemia in Early OvernutritionFigure 4. Gene expression of angiotensinogen (A), angiotensin receptor type 1a (AGTRa, (B)), angiotensin receptor type 2 (AGTR2, (C)) and pro-renin receptor (ATP6AP2, 
(D)) in.Vels were increased in the heart in response to both early overnutrition and I/R (P,0.01 and P,0.001 respectively, Figure 6B), with the levels of this anti-apoptotic protein being greater in overfed-IR rats than in control-IR (P,0.01).Inflammatory Markers in the MyocardiumiNOS content in the heart was unchanged in response to both early overfeeding and I/R. COX-2 levels were increased in the heart of overfed rats compared to controls (P,0.001, Figure 7A). I/R did not modify COX-2 levels in the heart of control rats but it decreased the levels of this protein in the heart of overfed rats (P,0.01, Figure 6B).DiscussionIn this study, we have used an experimental model of early overnutrition in rats by litter reduction in order to assess the effects of early overweight on cardiac function. As previously described, litter reduction increased food intake, and resulted in a higher weight gain and fat mass compared with control litters [28], [21,29,30]. This correlated with higher plasma levels of leptin in overfed rats. These alterations may be due, at least in part, to impaired response of neurons in arcuate and ventromedial hypothalamic nuclei to the anorexigenic effects of leptin andinsulin [23,31]as well as to altered metabolic activity of adipose tissue [32]. Previous studies had reported cardiovascular alterations in early overfed rats such an increase in blood pressure [32]and cardiac fibrosis [8]. However, to our knowledge this is the first study showing the deleterious effects of early overnutrition on cardiac function. These alterations could be due, at least in part, to changes in cardiomyocytes maturation as it is reported that this process in the rat takes place during late prenatal or early postnatal life [33]. In addition different perinatal insults, such as poor nutrition, hypoxia and endocrine stress are reported to alter this process inducing an alteration of the number of cells in the myocardium [34]. The perfused hearts from overfed rats showed reduced left ventricular developed pressure, which may be due to impaired myocardial contractility in those hearts. This myocardial impairment was accompanied by increased expression of apoptosis markers in the hearts of overfed rats. However it is interesting that antiapoptotic markers were also increased in this condition, which may constitute an attempt of compensation by myocardial cells. Expression of COX-2 was also increased in the hearts of early overfed rats. This enzyme isoform is induced in 15755315 inflammatory states, and therefore may be considered an inflammation marker. This apoptotic and inflammatory condition in hearts of overfed rats may damage myocardial cells and result in reduced contractility. In obese patients, increased cardiac output and systolic volume is usually observed, and this increase may be related to the higher blood flow needed as a result of higher body mass. However, when the difference in body weight is taken into account, obese subjects present reduced cardiac index and reduced myocardial contractility [35,36]. These alterations could be due to increased production of free radicals, inflammatory mediators and apoptotic markers in the heart [37]. Indeed, in the heart of Zucker obese rats, an increase in the levels of apoptotic markers such asEffects of Ischemia in Early OvernutritionFigure 4. Gene expression of angiotensinogen (A), angiotensin receptor type 1a (AGTRa, (B)), angiotensin receptor type 2 (AGTR2, (C)) and pro-renin receptor (ATP6AP2, (D)) in.
