ABSTRACT
AIM: In this study, the effects of postnatal overfeeding on heart energy homoeostasis and cardiac haemodynamics in adult male Swiss mice were examined. METHODS AND RESULTS: During the suckling period, the mice were divided into four groups of control or overfed pups in combination with baseline or ischaemia/reperfusion treatments (control group baseline, CGBL; overfed group baseline, OGBL; control group ischaemia/reperfusion, CGIR; and overfed group ischaemia/reperfusion, OGIR). End diastolic pressure (EDP), heart contraction speed (Max dP/dt), relaxation speed (Min dP/dt), isovolumetric relaxation time (Tau) and frequency by beats per minute (BPM) were measured. During baseline and ischaemia/reperfusion, key proteins such as AKT1, AKT2, AKT3, pAKT, adenosine monophosphate-activated protein kinase (AMPK), pAMPK, insulin receptor beta (IRß), protein tyrosine phosphatase 1B (PTP1B), insulin receptor substrate 1 (IRS1), fatty acid binding protein (FABP), CD36, phosphoinositide 3-kinase (PI3K) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) were studied. The expression of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), carnitine palmitoyltransferase 1 (CPT1) and uncoupling protein 3 (UCP3) was studied as a marker of cardiac hypertrophy and energetic metabolism. Cardiac fibrosis was analyzed by quantifying collagen deposition, which is increased in the OGBL and OGIR groups compared with the control groups. CONCLUSIONS: The OGBL group showed reduced EDP compared with the CGBL group and high Max dP/dt compared with the OGBL group. Ischaemia/reperfusion increased EDP and Min dP/dt in the intragroup comparison. By contrast, Tau and frequency were not significantly different among groups. The OGIR mice showed significant alterations in heart metabolism proteins, including AKT2, pAKT/AKT1, pAKT/AKT2, AMPK, pAMPK/AMPK, PTP1B, IRS1, FABP and CD36. Furthermore, alterations in ANP, BNP, CPT1 and UCP3 messenger RNA (mRNA) expression indicated hypertrophy and reduction in their efficiency, such that exclusive overnutrition in childhood induces a long-term effect on haemodynamics, metabolism and heart remodelling.
Subject(s)
Heart Failure/etiology , Lactation , Overnutrition/complications , Animals , Atrial Natriuretic Factor/genetics , Atrial Natriuretic Factor/metabolism , Blood Pressure , Female , Heart Failure/metabolism , Hemodynamics , Insulin Receptor Substrate Proteins/genetics , Insulin Receptor Substrate Proteins/metabolism , Intra-Abdominal Fat/metabolism , Ion Channels/genetics , Ion Channels/metabolism , Male , Mice , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Myocardial Contraction , Myocytes, Cardiac/metabolism , Overnutrition/metabolism , PPAR gamma/genetics , PPAR gamma/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Postnatal Care , Protein Tyrosine Phosphatase, Non-Receptor Type 1/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptor, Insulin/genetics , Receptor, Insulin/metabolism , Uncoupling Protein 3ABSTRACT
Overnutrition during pregnancy and lactation lend increasing support to the development of obesity and several chronic diseases in adulthood such as type 2 diabetes mellitus, which leads to beta-cell dysfunction and insulin resistance. In this work, we aimed to study the effects of early life overnutrition on the development of obesity, analyzing the morphological changes, expression of TNF-α, and also the stem cell marker CD133 in the pancreatic islets of young and adult mice. Overnutrition during lactation phase was used as an experimental model to induce obesity. The animals were analyzed at 28 and 150 days of age, when pancreata were collected for histological, ultrastructural and western blotting analysis. The results showed that islet hypertrophy is established in obese groups at day 28 and remained until adulthood. CD133+ cells were observed as small cells within pancreatic islets in both control and obese young mice. However, at day 150, these cells were observed only in the islet peripheries and near ducts of the obese group. Furthermore, TNF-α expression in pancreatic islets was increased in both young and adult obese groups when compared to control groups. This work shows interesting data about CD133 receptor and TNF-α roles in the pancreas during obesity development.
