ACE-modulated adiposity is related to higher energy expenditure and independent of lipolysis and glucose incorporation into lipids in adipocytes.

Emerging evidence suggests that both systemic and white adipose tissue-renin-angiotensin system components influence body weight control. We previously demonstrated that higher angiotensin-converting enzyme (ACE) gene expression is associated with lower body adiposity in a rodent model. In this study, we tested the hypothesis that a higher ACE gene dosage reduces fat accumulation by increasing energy expenditure and modulating lipolysis and glucose incorporation into lipids in adipocytes. After a 12 wk follow-up period, transgenic mice harboring three ACE (3ACE) gene copies displayed diminished WAT mass, lipid content in their carcasses, adipocyte hypotrophy, and higher resting oxygen uptake (V̇o2) in comparison with animals with one ACE gene copy (1ACE) after long fasting (12 h). No differences were found in food intake and in the rates of lipolysis and glucose incorporation into lipids in adipocytes. To assess whether this response involves increased angiotensin II type I receptor (AT1R) activation, AT1R blocker (losartan) was used in a separate group of 3ACE mice with body weight and adiposity comparable to that in the other 3ACE animals. We suggest that fasting-induced lower adiposity observed in animals with 3ACE gene copies might be associated with a higher expense of energy reserves; this response did not involve AT1R activation.

Effects of Aerobic Exercise Protocol on Genes Related to Insulin Resistance and Inflammation in the Pancreas of ob/ob Mice with NAFLD.

PURPOSE: To evaluate the effect of 8 weeks of aerobic training on insulin resistance and inflammatory response in obese mice (ob/ob) with NAFLD. MATERIALS AND METHODS: Male ob/ob mice were randomly divided into sedentary (n=7) and trained (n=7) groups. Aerobic training consisted of 5 weekly sessions, 60 min per session at 60% of the maximum speed of the running test. Hepatic and pancreatic samples were collected to evaluate histological features and gene expression associated with insulin resistance and inflammatory response after 8-week experiment protocol. RNA was performed by TRIzol®. PCR experiments were performed using the Rotor-Gene RG-3000. Parametric data were assessed by t-test, one-way ANOVA and Bonferroni test for multiple comparisons. Non-parametric data were assessed by the Mann-Whitney tests with Dunn's post-test of multiple comparisons. Histological analysis was assessed by chi-square test with Fisher's exact test. Significant variables were considered when p<0.05. All the analyses were performed by GraphPad Prism V6.0 software (GraphPad Software Inc.). RESULTS: Reductions in bodyweight (p = 0.008), weight evolution (p = 0.03), food intake (p <0.0001) and fat content were observed in trained group. Moreover, the trained group showed better results in peak velocity (p=0.03) physical effort tolerance (p=0.006) and distance (p=0.01). Gene expression showed differences in IL-10 (p=0.03) and GLUT-2 (p=0.03) in hepatic analysis, between groups. Pancreatic gene expression showed difference between groups in IRS-2 (p=0.004), GLUT-2 (p=0.03) and IL-10 (p=0.008) analysis. Also, the trained group showed lower values for interlobular fat and inflammatory infiltrate in histological analysis when compared to sedentary animals. CONCLUSION: An 8-week physical training protocol was able to attenuate bodyweight gain, food intake and generate positive effects on gene expression related to insulin resistance and inflammation in both liver and pancreas of ob/ob mice.

Early consumption of high-fat diet worsens renal damage in spontaneously hypertensive rats in adulthood.

The association between hypertension and obesity has been shown to be an important cause of kidney disease. We aimed to investigate the impact of a high-fat diet (HFD) administered in spontaneously hypertensive rats (SHR) after weaning in renal morphology and functional parameters. Male post-weaned SHR were divided into two groups: standard control diet (CD) (3% lipids; n = 8) or HFD (30% lipids; n = 8) during 8 weeks. The group HFD showed an increase in serum triglycerides (HFD: 96 ± 7 vs. CD: 33 ± 2 mg/dL) and glucose intolerance (HFD: 185 ± 7 vs. CD: 149 ± 4 mg/dL/min). Moreover, the HFD also showed an increase in almost 90% of the periepididymal and retroperitoneal adiposity. There was no difference in arterial blood pressure between groups. Renal morphofunctional parameters were decreased in HFD group for glomerular tuft area and diameter (4733 ± 65 µm2 and 82 ± 1 µm, respectively) when compared with CD group (5289 ± 171 µm2 and 88 ± 2 µm, respectively). HFD also showed a decrease of 50% of the renal function, which was associated with higher renal extracellular matrix and lipid deposition. Therefore, our data suggest that HFD since early period of life may contribute to renal damage in adults with hypertension, and this impairment can be associated with increased renal lipid accumulation.

Small gene effect and exercise training-induced cardiac hypertrophy in mice: an Ace gene dosage study.

Small gene effects influence complex phenotypes in a context dependent manner. Here we evaluated whether increasing dosage of the angiotensin I converting enzyme (Ace) gene influence exercise-induced cardiac hypertrophy. Mice harboring one, two, three, and four copies of the Ace gene were assigned to sedentary (S1-4) and swimming exercise-trained (T1-4) groups (1.5 h twice daily, 5 days/wk, 4 wk). Exercising resulted in comparable bradycardia and elevated skeletal muscle citrate synthase activity, while blood pressure remained unchanged. Left ventricle mass index and cardiomyocyte diameter were similar among sedentary mice and the magnitude of their increase associated to exercising was not influenced by the Ace genotype (T1: 12.6 and 17.9%, T2: 15.2 and 13.8%, T3: 16.9 and 20%, T4: 17 and 19%, respectively). Plasma renin activity (PRA) levels were higher in one vs. three or four copies mice (4.89 +/- 0.5 vs. 2.43 +/- 0.6 and 2.12 +/- 01.1 ng/ml Ang I, P < 0.05), while cardiac ACE activity was higher in three vs. two or one copy mice (5,946 +/- 590.8 vs. 2,951.5 +/- 328.3 and 3,504.1 +/- 258.9 microF x min(-1) x ml(-1), P < 0.05). With exercise, PRA remained unchanged in each group, while cardiac immunostaining for Ang II reached comparable levels. In summary: 1) exercise training led to similar aerobic adaptation regardless of the Ace genotype, and 2) higher number of Ace gene copies per se, which alters cardiac ACE activity, did not influence basal cardiac mass or, most importantly, the magnitude of swimming-induced cardiac hypertrophy. Collectively, these data indicate that small isolated genetic disturbances in ACE cardiac levels can be well compensated under physiological perturbations.

Repercussões do destreinamento físico no sistema cardiovascular, massa corporal e perfil lipídico / Repercussions of physical detraining on cardiovascular system, body mass and lipid profile

O presente manuscrito teve por objetivo a revisão de literatura sobre os efeitos do destreinamento (DT) no sistema cardiovascular e em fatores de risco cardiovasculares, tais como massa corporal, adiposidade e perfil lipídico. Para isso, uma ampla pesquisa da literatura nas bases de dados PubMed, Scopus e Web of Science foi realizada, e o conjunto de dados mostrou que o DT promove reversão das adaptações cardiovasculares obtidas com o treinamento físico, tais como redução do VO2máx, do débito cardíaco máximo, do volume sistólico, do volume sanguíneo e da massa ventricular. Além disso, o DT induz aumento da frequência cardíaca de repouso e submáxima, da resistência vascular periférica e da pressão arterial. O curso temporal para que tais efeitos cardiovasculares ocorram é amplo, podendo ocorrer a partir da segunda semana de DT até três meses após o DT. O DT também gera prejuízos aos fatores de risco cardiovasculares, tais como aumento da massa corporal e da adiposidade, aumento do colesterol total, LDL e VLDL, e redução do HDL. Enquanto os efeitos na massa corporal aparecem após quatro semanas de DT, as mudanças no perfil lipídico são mais precoces, com apenas uma semana de DT

The objective of this manuscript is to review the literature about the effects of detraining (DT) on the cardiovascular system and on cardiovascular risk factors such as body mass, adiposity and lipid profile. For this, a wide literature search in the PubMed, Scopus and Web of Science databases was performed, and the data showed that DT promotes the reversal of cardiovascular adaptations obtained with physical training, such as reduction in VO2 max, cardiac output, ejection fraction, blood volume and ventricular mass. In addition, DT induces an increase in resting and submaximal heart rates, peripheral vascular resistance and blood pressure. The timeframe for such cardiovascular effects to be seen is long, which may occur from the second week of DT to 3 months after DT. DT also causes damage to cardiovascular risk factors by inducing an increase in body mass and adiposity, an increase in total cholesterol, LDL and VLDL, and a reduction in HDL. While effects on body mass appear after 4 weeks of DT, changes in lipid profile appear earlier, with only 1 week of DT

Comparison between cafeteria and high-fat diets in the induction of metabolic dysfunction in mice.

This study sought to compare the metabolic responses induced by high-fat (HF) diet and cafeteria (CA) diet in mice. Adult male C57BL/6J mice were assigned into groups fed a chow (C, n=13), CA (n=12) or HF (n=11) diet during 12 weeks. Diets did not change body weight, Lee index, inguinal subcutaneous fat, the weight of organs and muscles, resting arterial pressure and heart rate. CA and HF increased visceral fat pad mass compared to C group, but only CA group showed greater adipocyte diameter and food intake compared to the C. Food intake was reduced in HF compared to C group. CA and HF showed hyperglycemia in the 3(rd), 6(th), 9(th) and 12(th) week and all values were higher in CA than HF, except in the 6(th) week. CA group showed glucose intolerance (GI) in the 6(th) week, while HF group did not show GI until the 9(th) week. CA decreased insulin sensitivity compared to C in the 12(th) week (kITT=3.3±0.2%/min vs. 4.2±0.1%/min). CA and HF groups presented higher insulin, leptin, total cholesterol, LDL-C, triglycerides and FFA levels compared to the C group. Total cholesterol and LDL-C in mg/dL were higher in the HF (161.9±7.2 and 57.5±13.4) than the CA (110.5±9.1 and 48.5±11.4), and HDL-C was higher in the HF than in the C and CA groups. In conclusion, the CA diet was more efficient to induce hyperphagia, adipocyte hypertrophy, hyperglycemia, earlier GI and insulin resistance, while the HF diet was more efficient to induce lipid profile changes.

The effects of green tea consumption on cardiometabolic alterations induced by experimental diabetes.

We evaluated cardiac autonomic modulation by heart rate (HRV), and arterial pressure variability (APV), and metabolic response in streptozotocin diabetic rats treated with green tea. Male Wistar rats were separated in groups: control, drinking tap water (C), green tea-treated (GT) group, diabetic, drinking tap water (D), and diabetic, treated with green tea (DGT). Kidney mass was greater in D and DGT than in C and GT, but reduced in DGT compared to D. Green tea prevented the increase in creatinine clearance and reduced hyperglycemia in DGT compared to D. Arterial pressure was increased in GT and decreased in D compared to C. HRV was reduced in D compared with all groups. APV was decreased in D compared to C and recovery in DGT. Sympathetic modulation of APV was decreased in D compared with all groups. Green tea reduced hyperglycemia, prevented renal injury and autonomic dysfunction, suggesting reduced cardiovascular risk and target organ damage in diabetes.