RESUMO
OBJECTIVE: To evaluate the impact of a short-term cardiovascular physical programme on the metabolic, anthropometric and oxidative stress parameters of women with metabolic syndrome. METHODS: Thirty sedentary female patients, age range 30-60 years, were invited to participate in a 6-week cardiovascular physical programme. The training consisted of 60-min sessions of aerobic and strength exercises performed 3 times a week; a total of 18 sessions. Anthropometric data, functional exercise capacity, general biochemical profile, serum lipid peroxidation, superoxide dismutase and catalase activity in erythrocytes were evaluated according to standardized protocols. Peripheral vascular function was assessed using applanation tonometry. All assessments were performed before and after the training programme. RESULTS: The physical programme proved effective in improving the distance covered in the 6-min walk test and in reducing arterial pressure levels, pulse pressure and the Augmentation Index, without modifying heart rate. The plasma thiobarbituric acid reactive substances levels, indicators of oxidative stress, were significantly decreased after the programme. Superoxide dismutase activity was increased in erythrocyte lysates, with no significant change in catalase activity. Waist circumference was significantly decreased compared with baseline. The distance covered in the 6-min walk test was significantly greater after the short-term cardiovascular training. CONCLUSION: These findings indicate that short-term combined aerobic and strength training may represent an important non-pharmacological approach for treating individuals with metabolic syndrome.
Assuntos
Terapia por Exercício/métodos , Síndrome Metabólica/fisiopatologia , Síndrome Metabólica/reabilitação , Estresse Oxidativo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Rigidez Vascular , Adulto , Antropometria , Biomarcadores/metabolismo , Pressão Sanguínea , Exercício Físico , Feminino , Hemodinâmica , Humanos , Peroxidação de Lipídeos , Manometria , Pessoa de Meia-Idade , Treinamento Resistido , Superóxido Dismutase/metabolismo , Circunferência da Cintura , CaminhadaRESUMO
The renin-angiotensin (Ang) system (RAS) plays an important role in the control of glucose metabolism and glycemia. Several studies demonstrated that the effects of angiotensin-(1-7) are mainly opposite to the actions of biological angiotensin II. Recent studies have demonstrated that rats with increased circulating angiotensin-(1-7), acting through the G protein coupled receptor Mas, have enhanced glucose tolerance and insulin sensitivity, presenting improved metabolic parameters. However, there is no data regarding the role of angiotensin-(1-7)-Mas axis in hepatic glycemic metabolism. In the present study, the gluconeogenesis and glycogenolysis was investigated in Sprague-Dawley (SD) and in TGR(A1-7)3292 (TGR) rats which present approximately twofold increase in plasma Ang-(1-7) levels compared to SD. The pyruvate administration in fasted rats showed a decreased synthesis of glucose in TGR compared to the SD rats, pointing to a downregulation of gluconeogenesis. Supporting this data, the mRNA evaluation of gluconeogenic enzymes showed a significant reduction in phosphoenolpyruvate carboxykinase reinforced by a significantly diminished expression of hepatocyte nuclear factor 4α (HNF-4α), responsible for the regulation of gluconeogenic enzymes. In conclusion our data show that the improved glucose metabolism induced by Ang-(1-7) could be due, at least in part, to a downregulation of hepatic gluconeogenesis.
Assuntos
Angiotensina I/sangue , Gluconeogênese , Fígado/metabolismo , Fragmentos de Peptídeos/sangue , Animais , Ratos , Ratos Sprague-Dawley , Ratos TransgênicosRESUMO
INTRODUCTION: The aim of the present study was to evaluate the effect of a transgenic-induced chronic increase of Ang-(1-7) on the expression of inflammatory markers in adipose tissue and the metabolic profile in rats treated with high-fat diet. RESEARCH DESIGN AND METHODS: Transgenic rats expressing an Ang-(1-7)-producing fusion protein (TGR L-3292) and Sprague Dawley (SD) control rats 4 weeks old were treated for 8 weeks with a high-fat diet. Food intake and body weight were measured once a week. Glucose-tolerance and insulin sensitivity tests were performed one week before the sacrifice. At the end of the experiment plasma lipid concentrations were measured in TGR and SD rats. Adipose tissue were weighted and corrected by the body weight. Proinflammatory markers in adipose tissue were analyzed using Western-blotting, real time-PCR and immunohistochemistry. RESULTS: High-fat diet TGR rats presented increased HDL cholesterol levels and decreased abdominal fat mass, without changes in food intake. In addition, rats with increased Ang-(1-7) levels had lower body weight. Molecular analysis revealed decreased IL-1ß and COX-2 in adipose tissue. CONCLUSIONS: Taken together, these results show that chronic high circulating angiotensin-(1-7) levels protect against metabolic stress induced by a high-fat diet decreasing the proinflammatory profile of adipose tissue.
Assuntos
Angiotensina I/sangue , Dieta Hiperlipídica/efeitos adversos , Mediadores da Inflamação/metabolismo , Gordura Intra-Abdominal/patologia , Fragmentos de Peptídeos/sangue , Adipocinas/sangue , Adiposidade , Animais , Glicemia , HDL-Colesterol/sangue , Epididimo/metabolismo , Epididimo/patologia , Inflamação , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Gordura Intra-Abdominal/metabolismo , Masculino , Obesidade/sangue , Obesidade/etiologia , Obesidade/patologia , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Previous evidence indicates that a balance between inhibitory gabaergic and excitatory angiotensinergic factors in the PVN is important for cardiovascular control. We investigated the cardiovascular response evoked from activation or blockade of GABA(A) receptors in the paraventricular nucleus (PVN), in transgenic rats with low brain angiotensinogen [TGR(ASrAOGEN)]. Brain Ang II and Ang-(1-7) levels were also determined. In functional experiments, TGR(ASrAOGEN) and Sprague-Dawley rats (SD, control) were anesthetized with urethane and blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded. Brain Ang II and Ang-(1-7) levels were largely reduced in TGR(ASrAOGEN) compared with SD rats. Inhibition of PVN neurons with the GABA(A) agonist, muscimol (1 nmol/100 nL), resulted in an attenuated fall in all cardiovascular variables in TGR(ASrAOGEN) compared with SD rats. This difference was particularly pronounced in HR (TGR Mus -23±6 bpm vs. -77±9 bpm SD Mus; P<0.05) and RSNA (TGR -3±10% vs.-29±8% SD; P<0.05). Furthermore, the sympathetic response evoked by blockade of GABA(A) receptors in the PVN of TGR(ASrAOGEN) was also largely suppressed. The present data indicate that the sympathetic outflow mediated by PVN neurons under basal conditions is suppressed in TGR(ASrAOGEN) rats corroborating the functional significance of brain angiotensin production in the central regulation of sympathetic output to the cardiovascular system.
Assuntos
Angiotensinogênio/deficiência , Química Encefálica/efeitos dos fármacos , Agonistas GABAérgicos/farmacologia , Antagonistas GABAérgicos/farmacologia , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Receptores de GABA-A/fisiologia , Animais , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Química Encefálica/genética , Expressão Gênica/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Compostos de Hexametônio/farmacologia , Rim/inervação , Rim/fisiologia , Radioimunoensaio , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Sistema Nervoso Simpático/fisiologia , Transgenes/genéticaRESUMO
The renin-angiotensin system is an important link between metabolic syndrome and cardiovascular diseases. Besides angiotensin II, other angiotensin peptides such as angiotensin-(1-7), have important biological activities. It has been demonstrated that angiotensin-(1-7), acting through the G protein-coupled receptor encoded by the Mas protooncogene have important actions on the cardiovascular system. However, the role of angiotensin-(1-7)-Mas axis in lipidic profile is not well established. In the present study, the adipocyte metabolism was investigated in wild type and FVB/N Mas-deficient male mice. The gene expression of peroxisome proliferator-activated receptor gamma, acetyl-CoA carboxylase and the amount of fatty acid synthase protein were reduced in the Mas-knockout mice. Serum nonesterified fatty acids of Mas-knockout showed a 50% increase in relation to wild type group. Basal and isoproterenol-stimulated lipolysis was similar between the groups, however, a significant decrease of the glycerol release (lipolytic index) in response to insulin was observed in wild type animals, while no effect of the insulin action was observed in a Mas-knockout group. The data suggest that the lack of angiotensin-(1-7) action through Mas receptor alters the response of adipocytes to insulin action. These effects might be related to decreased expression of PPARγ.
Assuntos
Adipócitos/fisiologia , PPAR gama/genética , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Adipócitos/efeitos dos fármacos , Tecido Adiposo , Animais , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Ácidos Graxos não Esterificados/sangue , Regulação da Expressão Gênica , Glicerol/metabolismo , Insulina/farmacologia , Isoproterenol/farmacologia , Lipólise/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , PPAR gama/metabolismo , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/genética , Receptores Acoplados a Proteínas G/genéticaRESUMO
OBJECTIVE: Obesity and diabetes remain among the world's most pervasive health problems. Although the importance of angiotensin II for metabolic regulation is well documented, the role of the angiotensin-(1-7)/Mas axis in this process is poorly understood. The aim of this study was to evaluate the effect of increased angiotensin-(1-7) plasma levels in lipid and glucose metabolism using transgenic rats that express an angiotensin-(1-7)-releasing fusion protein, TGR(A1-7)3292 (TGR). METHODS AND RESULTS: The increased angiotensin-(1-7) levels in TGR induced enhanced glucose tolerance, insulin sensitivity, and insulin-stimulated glucose uptake. In addition, TGR presented decreased triglycerides and cholesterol levels, as well as a significant decrease in abdominal fat mass, despite normal food intake. These alterations were accompanied by a marked decrease of angiotensinogen expression and increased Akt in adipose tissue. Furthermore, augmented plasma levels and expression in adipose tissue was observed for adiponectin. Accordingly, angiotensin-(1-7) stimulation increased adiponectin production by primary adipocyte culture, which was blocked by the Mas antagonist A779. Circulating insulin and muscle glycogen content were not altered in TGR. CONCLUSION: These results show that increased circulating angiotensin-(1-7) levels lead to prominent changes in glucose and lipid metabolism.
Assuntos
Tecido Adiposo/metabolismo , Angiotensina II/sangue , Glicemia/metabolismo , Metabolismo dos Lipídeos , Fragmentos de Peptídeos/sangue , Adipócitos/metabolismo , Adiponectina/sangue , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Adiposidade , Angiotensina I , Angiotensina II/análogos & derivados , Angiotensina II/genética , Angiotensina II/farmacologia , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Peso Corporal , Células Cultivadas , Colesterol/sangue , Insulina/sangue , Leptina/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Masculino , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/farmacologia , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/metabolismo , Fatores de Tempo , Triglicerídeos/sangue , Regulação para CimaRESUMO
OBJECTIVE: Metabolic syndrome is characterized by the variable coexistence of obesity, hyperinsulinemia, insulin resistance, dyslipidemia, and hypertension. It is well known that angiotensin (Ang) II is importantly involved in the metabolic syndrome. However, the role of the vasodilator Ang-(1-7)/Mas axis is not known. The aim of this study was to evaluate the effect of genetic deletion of the G protein-coupled receptor, Mas, in the lipidic and glycemic metabolism in FVB/N mice. RESEARCH DESIGN AND METHODS: Plasma lipid, insulin, and cytokine concentrations were measured in FVB/N Mas-deficient and wild-type mice. A glucose tolerance test was performed by intraperitoneally injecting d-glucose into overnight-fasted mice. An insulin sensitivity test was performed by intraperitoneal injection of insulin. Uptake of 2-deoxy-[(3)H]glucose by adipocytes was used to determine the rate of glucose transport; adipose tissue GLUT4 was quantified by Western blot. Gene expression of transforming growth factor (TGF)-beta, type 1 Ang II receptor, and angiotensinogen (AGT) were measured by real-time PCR. RESULTS: Despite normal body weight, Mas-knockout (Mas-KO) mice presented dyslipidemia, increased levels of insulin and leptin, and an approximately 50% increase in abdominal fat mass. In addition, Mas gene-deleted mice presented glucose intolerance and reduced insulin sensitivity as well as a decrease in insulin-stimulated glucose uptake by adipocytes and decreased GLUT4 in adipose tissue. Mas(-/-) presented increased muscle triglycerides, while liver triglyceride levels were normal. Expression of TGF-beta and AGT genes was higher in Mas-KO animals in comparison with controls. CONCLUSIONS: These results show that Mas deficiency in FVB/N mice leads to dramatic changes in glucose and lipid metabolisms, inducing a metabolic syndrome-like state.
Assuntos
Glicemia/metabolismo , Insulina/sangue , Lipídeos/sangue , Proteínas Proto-Oncogênicas/deficiência , Receptores Acoplados a Proteínas G/deficiência , Adipócitos/metabolismo , Tecido Adiposo/anatomia & histologia , Tecido Adiposo/fisiologia , Animais , Transporte Biológico , Peso Corporal , Citocinas/sangue , Ingestão de Energia , Epididimo/patologia , Glucose/metabolismo , Teste de Tolerância a Glucose , Masculino , Síndrome Metabólica/genética , Síndrome Metabólica/patologia , Camundongos , Camundongos Knockout , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/genética , Receptores Acoplados a Proteínas G/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Triglicerídeos/sangueRESUMO
The aim of the present study was to evaluate plasma renin activity (PRA) and Angiotensin (Ang) levels [Ang I, Ang II and Ang-(1-7)] to examine the circulating Renin-Angiotensin System (RAS) in renal disease among children with different forms and stages of chronic renal failure (CRF). Subjects were divided as follows: 32 normotensive healthy subjects, 23 normotensive CRF subjects, 34 hypertensive CRF subjects and 21 subjects with end-stage renal disease (ESRD). Radioimmunoassays for PRA (ngAngI/mL/h) and angiotensin (pg/mL) measurements were performed on all subjects. PRA, Ang I, Ang II and Ang-(1-7) levels were significantly higher in hypertensive CRF subjects when compared with normotensive CRF and healthy subjects (p < 0.05 for all comparisons). No differences were observed between normotensive CRF and healthy subjects. ESRD subjects exhibited a dramatic increase in Ang-(1-7) (25-fold higher than control values). In hypertensive CRF subjects, treatment with angiotensin-converting enzyme inhibitors (ACEi) increased (1.4-fold) plasma Ang-(1-7) and decreased (2.4-fold) Ang II. In ESRD, the use of ACEi produced a similar (1.5-fold) elevation of Ang-(1-7), but no changes in plasma Ang II. Our data showed different circulating RAS profiles between hypertensive and in normotensive CRF subjects. Marked changes in plasma Ang-(1-7) were associated with the presence of hypertension and progression of kidney dysfunction.