0004). Blood glucose was 34% higher in SL than in NL group (P < 0.0004). To investigate circulating levels of acylated ghrelin, we measured these after 4 h of fasting. SL group presented significantly decreased plasma acylated ghrelin levels (98.64 ± 23.1 pg/mL) compared with NL mice (201.1 ± 20.7 pg/mL) (p < 0.01) ( Table 1). Many biological actions of ghrelin are started by the binding of ghrelin to its cognate cell surface receptor GHSR-1a [53]. SL animals had a markedly higher (2.9-fold) GHSR-1a content than their counterparts (P < 0.0004) ( Fig. 5A and B), and higher PI3K association with GHSR-1a in SL than NL groups (P < 0.05) ( Fig. 5B). In addition, GHSR-1a mRNA was increased in SL-hearts as compared

to NL ventricles (P < 0.05, Fig. 6). We examined the basal phosphorylation state of AKT-Ser473 in the left ventricles of NL and SL mice (Fig. 7). Fig. 7A shows that AKT content in SL mTOR inhibitor mice was 42.7% higher when compared to NL mice (P < 0.03). Furthermore, AKT was highly phosphorylated in left ventricles of SL mice (57.1%), when compared to NL mice ( Fig. 7B). We investigated AMPK content and activation. Fig. 8(A and B), shows that there were no significant difference among the groups with respect to AMPK content and phosphorylation. Early life overnutrition induced Olaparib supplier a significant increase in body weight in adult mice. This observation confirms previous results from our and other groups [9],

[26], [28], [35] and [37]. Basically, obesity resulted in a significant accumulation of retroperitoneal and epididymal fat masses when the mice reach adulthood. In addition, we observed increased ratio of body weight to tibia length in early life overnourished

mice, showing that the difference between groups was in body weight, not in length. In others words, early life overnutrition induced a metabolic profile where energy storage was privileged. Thus, these data reinforces the theory that the development of obesity, diabetes, and cardiovascular disease IKBKE is an expected output in adulthood of the animals submitted to disturbed nutrition in early life [9], [26], [28], [35], [37] and [45]. Therefore, we hypothesized that in hearts of these obese mice, the signaling process of the gut-derived hormone ghrelin should be altered. In this context to explain this process we firstly showed the presence of the ghrelin receptor GHSR-1a in left ventricles confirming results from other authors [8]. And, as original data, we clearly demonstrated that obesity induced in early life increases heart ghrelin receptor expression (GHSR-1a) in adulthood. In other words, these result confirmed evidences indicating that cardiovascular tissue is rich in ghrelin receptors, reinforcing results in the literature in which increases are found in ghrelin receptor mRNA of human cardiomyocytes, rat cardiomyocytes and cardiovascular vessels [13].