Oral Ang-(1-7) treatment improves white adipose tissue remodeling and hypertension in rats with metabolic syndrome.

Objective: Angiotensin (Ang)-(1-7) has preventive effects on metabolic syndrome (MetS). The aim of this study was to evaluate the therapeutic effect of oral Ang-(1-7) on mean arterial pressure (MAP), insulin resistance (IR), inflammatory process, and remodeling of white adipose tissue (WAT) in rats with establishedMetS. Methods: Rats were subjected to control (CT; AIN-93M) or high-fat (HF) diets for 13 wk to induce MetS and treated with Ang-(1-7) or vehicle (V) for the last 6 wk. At the end of 13 wk, MAP, biochemical and histological parameters, and uncoupling protein (UCP) and inflammatory gene expression were determined by quantitative reverse transcription polymerase chain reaction. Results: HF-V rats showed increased visceral fat deposition, inflammatory cytokine expression, hyperplasia, and hypertrophy in retroperitoneal (WAT) and brown adipose tissue (BAT). Additionally, the gastrocnemius muscle reduced UCP-3 and increased the UCP-1 expression in BAT. HF-V also elevated levels of plasma insulin, glucose, homeostatic model assessment (HOMA) of IR and HOMA-b, and increased body mass, adiposity, and MAP. Ang-(1-7) treatment in rats with MetS [HF-Ang-(1-7)] reduced WAT area, number of adipocytes, and expression of proinflammatory adipokines in WAT and BAT and increased UCP-3 in gastrocnemius muscle and UCP-1 expression in BAT compared with the HF-V group. These events prevented body mass gain, reduced adiposity, and normalized fasting plasma glucose, insulin levels, HOMA-IR, HOMA-b, and MAP. Conclusion: Data from the present study demonstrated that oral Ang-(1-7) treatment is effective in restoring biochemical parameters and hypertension in established MetS by improving hypertrophy and hyperplasia in WAT and inflammation in adipose tissue, and regulating metabolic processes in the gastrocnemius muscle and BAT

Antioxidant effects of oral Ang-(1-7) restore insulin pathway and RAS components ameliorating cardiometabolic disturbances in rats.

In prevention studies of metabolic syndrome (MetS), Ang-(1-7) has shown to improve the insulin signaling. We evaluated the HP?CD/Ang-(1-7) treatment on lipid metabolism, renin-angiotensin system (RAS) components, oxidative stress, and insulin pathway in the liver and gastrocnemius muscle and hepatic steatosis in rats with established MetS. After 7 weeks of high-fat (FAT) or control (CT) diets, rats were treated with cyclodextrin (HP?CD) or HP?CD/Ang-(1-7) in the last 6 weeks. FATHP?CD/ empty rats showed increased adiposity index and body mass, gene expression of ACE/ANG II/AT1R axis, and oxidative stress. These results were accompanied by imbalances in the insulin pathway, worsening of liver function, hyperglycemia, and dyslipidemia. Oral HP?CD/Ang-(1-7) treatment decreased ACE and AT1R, increased ACE2 gene expression. in the liver, and restored thiobarbituric acid reactive substances (TBARS), catalase (CAT), superoxide dismutase (SOD), insulin receptor substrate (Irs-1), glucose transporter type 4 (GLUT4), and serine/threonine kinase 2 (AKT-2) gene expression in the liver and gastrocnemius muscle improving hepatic function, cholesterol levels, and hyperglycemia in MetS rats. Overall, HP?CD/Ang-(1-7) treatment restored the RAS components, oxidative stress, and insulin signaling in the liver and gastrocnemius muscle contributing to the establishment of blood glucose and lipid homeostasis in MetS rats

Efeito terap?utico do treinamento f?sico na s?ndrome metab?lica induzida por dieta hiperlip?dica em ratos.

Programa de P?s-Gradua??o em Sa?de e Nutri??o. Escola de Nutri??o, Universidade Federal de Ouro Preto.A s?ndrome metab?lica (SM) ? caracterizada pela coexist?ncia de altera??es metab?licas como ac?mulo de tecido adiposo branco visceral, resist?ncia ? insulina, dislipidemias, hipertens?o arterial, disfun??o endotelial e estado pr?-inflamat?rio. O treinamento f?sico (TF) tem sido reconhecido por prevenir o desenvolvimento da SM por reduzir o tecido adiposo branco e aumentar os dep?sitos de tecido adiposo marrom (TAM), a sensibilidade perif?rica ? insulina e o gasto energ?tico. Por?m, poucos estudos t?m descrito a respeito da efici?ncia do TF no tratamento da SM. O objetivo desse estudo foi avaliar o efeito terap?utico do TF sobre os par?metros bioqu?micos, express?o de adipocinas e sinaliza??o da insulina no tecido adiposo retroperitoneal e no TAM, al?m de avaliar a express?o g?nica das prote?nas desacopladoras (UCPs) no m?sculo gastrocn?mico e no tecido adiposo em ratos com SM induzida pela dieta hiperlip?dica. Ratos com 4 semanas de idade foram alimentados com dieta controle AIN-93 ou dieta hiperlip?dica por 13 semanas e submetidos submetidos ao TF por seis semanas, a partir da s?tima semana de dieta, o TF consistia em nata??o com carga de at? 2,5% do peso corporal. A temperatura corporal e a ingesta alimentar foram quantificados semanalmante. A avalia??o indireta da press?o arterial m?dia (PAM) atrav?s de pletismografia de cauda foi realizada ao final da 6? e 13? semana. No final da 13? semana foi avaliado tamb?m a cin?tica do lactato sangu?neo (kit comercial), os par?metros bioqu?micos em soro e plasma usando kits comerciais e as express?es de mRNA (qRT-PCR) foram avaliadas no tecido adiposo retroperitoneal, no BAT e no m?sculo gastrocn?mico. Os animais SM-SED (17.1?0.8 mmol/L; n=6) apresentaram n?veis de lactato maior comparados ao grupo CT-SED (9.7?1.0 mmol/L; n=6). O grupo SM-TF (8.9?0.58 n=6) apresentou redu??o comparada ao grupo SM-SED e similar ao grupo CT-SED. N?o foi observado diferen?a entre os grupos (CT-SED e SM-SED). Os animais do grupo SM-TF apresentaram aumento da temperatura corporal cinco minutos antes do TF e redu??o cinco minutos ap?s o TF na 11? e12? quando comparados ao grupo CT-TF. J?, na 13? semana o grupo SM-TF cinco minutos antes e ap?s o TF o CT-TF cinco minutos ap?s apresentaram IX redu??o da temperatura corporal quando comparado ao grupo CT-TF cinco minutos antes do TF. Os animais dos grupos SM-SED e SM-TF apresentaram redu??o da ingesta alimentar comparados ao grupo CT-SED na 6?, 9? e 12? semana. Os animais dos grupos SM-SED e SM-TF apresentaram aumento da PAM e FC comparados ao grupo CT-SED na 6? semana. J? na 13? semana, os animais do grupo SM-SED apresentaram um aumento da press?o arterial e frequ?ncia card?aca comparados ao grupo CT-SED. E, al?m disso, houve uma redu??o da PAM no grupo SMTF comparado ao grupo SM-SED. Os animais SM-SED quando comparados ao grupo CT-SED, apresentaram aumento do peso corporal (316?9,6 g vs 286 ? 6,3 g), do ?ndice de adiposidade (7.8 ? 0.7 vs 4.4?0.2), dos n?veis plasm?ticos (mmol/L) de glicose de jejum (6.95?0.11 vs 6.16?0.15), do colesterol total (1.98?0.07 vs 1.76?0.04). Os animais que foram submetidos ? dieta hiperlip?dica e ao TF quando comparados ao grupo SM-SED apresentaram diminui??o do ?ndice de adiposidade (4.4?0.2 vs 6.1?0.3), do HOMA IR (9.1?1.8 vs 15.5?2.4), da leptina (2.7?0.4 vs 17.9?5.9), da resistina (1.7?0.8 vs 9.9?3.4), da adpisina (7.7?0.8 vs 35.3?10.4), do COX-2 (0.02?0.01 vs 0.13?0.04) no tecido adiposo retroperitoneal e aumento do TAM (0.31?0.02g vs 0.12?0.01g) e da UCP3 (3.55?1.37 vs 0.001?9.48) no m?sculo gastrocn?mico. Nossos dados mostraram que o TF foi eficiente como tratamento por reverter diferentes altera??es metab?licas e biom?tricas no tecido adiposo retroperitoneal e aumentar a atividade termog?nica do TAM de ratos com SM j? estabelecida induzida por dieta hiperlip?dica.Metabolic Syndrome is characterized by the presence of metabolic disorders such as visceral white adipose tissue accumulation, insulin resistance, dyslipidemia, hypertension, endothelial dysfunction and proinflammatory state. The physical training has been recognized for preventing the development of metabolic syndrome to reduce the white adipose tissue and increase deposits of brown adipose tissue, peripheral insulin sensitivity and energy expenditure. However, there are no data in the literature regarding physical training efficiency in the treatment of metabolic syndrome. The aim of this study was to evaluate the therapeutic effect of physical training on the biochemical parameters, adipokines expression and insulin signaling in retroperitoneal adipose tissue and the brown adipose tissue and to evaluate the gene expression of uncoupling proteins (UCPs) in the gastrocnemius muscle and adipose tissue in rats with metabolic syndrome induced by high fat diet. Rats with 4 weeks of age were fed with AIN-93 diet control or fat diet for 13 weeks and the physical training for six weeks from the seventh week of the diet, animals were swimming with loading up to 2.5% of body weight. The body temperature and food intake were measured semanalmante. The indirect measurement of mean arterial pressure by tail plethysmography was performed at the end of the 6th and 13th week. At the end of the 13th week was also evaluated the kinetics of blood lactate (commercial kit), biochemical parameters in serum and plasma using commercial kits and mRNA expression (qRT-PCR) were evaluated in the retroperitoneal adipose tissue, BAT and muscle gastrocnemius. SM-SED animals (17.1 ? 0.8 mmol/L; n = 6) showed higher levels of lactate compared to CT-SED group (9.7 ? 1.0 mmol/L; n = 6). The SM-TF group (8.9 ? 0.58 n = 6) showed a decrease compared to the SM-SED group and similar to CT-SED group. There was no difference between groups (CT-SED and SM-SED). Animals SM-TF group showed an increase in body temperature five minutes before physical training and reduced five minutes after the physical training, the 11th, 12th when compared to CT-TF group. Already, in the 13th week the SM-TF group five minutes before and after physical training and CT- TF five minutes after decreased body temperature hen compared to CT-TF group five minutes XI before the physical training. Animal SM-SED and SM-TF groups showed reduced food intake compared to the CT-SED group in 6th, 9th and 12th week, respectively. The animals of the SM-SED and SM-TF groups showed an increase in mean arterial pressure and cardiac frequency compared to CT-SED group at 6 weeks. In the 13th week, the animals of the SM-SED group had an increase in blood pressure and heart rate compared to CT-SED group. And besides, there was a reduction in blood pressure in the SM-TF group compared to the SM-SED group. SM-SED animals when compared to CT-SED group showed an increase in body weight (316 ? 9.6 g vs. 286 ? 6.3 g) of fat index (7.8 ? 0.7 vs 4.4 ? 0.2) in plasma levels (mmol/L) fasting glucose (6.95 ? 0.11 vs 6.16 ? 0.15), total cholesterol (1.98 ? 0.07 vs 1 76 ? 0.04). The animals were subjected to high-fat diet and physical training compared to SM-SED group showed decreased adiposity index (4.4 ? 0.2 vs 6.1 ? 0.3), HOMA IR (9.1 ? 1.8 vs 15.5 ? 2.4), leptin (2.7 ? 0.4 vs 17.9 ? 5.9) of resistin (1.7 ? 0.8 vs 9.9 ? 3 4) of adpisina (7.7 ? 0.8 vs. 35.3 ? 10.4), COX-2 (0.02 ? 0.01 vs 0.13 ? 0.04) in the retroperitoneal adipose tissue and increased brown adipose tissue (0.31 ? 0.02 g vs 0.12 ? 0.01 g) and UCP3 (3.55 ? 1.37 vs 0.001 ? 9.48) in the gastrocnemius muscle. Our data showed that the physical training was effective as a treatment to reverse different metabolic and biometric changes in retroperitoneal adipose tissue and increase the thermogenic activity of brown adipose tissue rats with metabolic syndrome already established induced by high fat diet

Maternal high-fat diet triggers metabolic syndrome disorders that are transferred to first and second offspring generations.

A high-fat (H) diet increases metabolic disorders in offspring. However, there is great variability in the literature regarding the time of exposure, composition of the H diets offered to the genitors and/or offspring and parameters evaluated. Here, we investigated the effect of a H diet subjected to the genitors on different cardio-metabolic parameters on first (F1)- and second (F2)-generation offspring. Female Fischer rats, during mating, gestation and breast-feeding, were subjected to the H diet (G0HF) or control (G0CF) diets. Part of F1 offspring becomes G1 genitors for generating the F2 offspring. After weaning, F1 and F2 rats consumed only the C diet. Nutritional, biometric, biochemical and haemodynamic parameters were evaluated. G0HF genitors had a reduction in food intake but energy intake was similar to the control group. Compared with the control group, the F1H and F2H offspring presented increased plasma leptin, insulin and fasting glucose levels, dietary intake, energy intake, adiposity index, mean arterial pressure, sympathetic drive evidenced by the hexamethonium and insulin resistance. Our data showed that only during mating, gestation and breast-feeding, maternal H diet induced cardio-metabolic disorders characteristic of human metabolic syndrome that were transferred to both females and males of F1 and F2 offspring, even if they were fed control diet after weaning. This process probably occurs due to the disturbance in mechanisms related to leptin that increases energy intake in F1H and F2H offspring. The present data reinforce the importance of balanced diet during pregnancy and breast-feeding for the health of the F1 and F2 offspring

Physical training improves thermogenesis and insulin pathway, and induces remodeling in white and brown adipose tissues.

Physical training (PT) has been considered as a treatment in metabolic syndrome (MS), since it induces thermogenic activity in brown (BAT) and white (WAT) adipose tissues. We evaluated the therapeutic effect of PT on activity of WAT and BAT in rats with MS induced by high-fat diet (30% lard) for 13 weeks and submitted, for the last 6 weeks, to swimming or kept sedentary (SED) rats. MS-SED rats compared to control diet (CT-SED) rats showed low physical fitness and high levels of glucose, insulin, homeostasis evaluation of insulin resistance (HOMA-IR), homeostasis evaluation of the functional capacity of ?-cells (HOMA-?), and blood pressure. The gastrocnemius muscle decreased in peroxisome proliferator-activated receptor gamma coactivator 1-alpha and beta (PGC-1?, PGC-1?), and uncoupled protein 2 and 3 (UCP2 and UCP3) expressions. Both WAT and BAT increased in the adipocyte area and decreased in blood vessels and fibroblast numbers. WAT increased in expression of pro-inflammatory adipokines and decreased in anti-inflammatory adipokine and adiponectin. WAT and gastrocnemius showed impairment in the insulin signaling pathway. In response to PT, MS rats showed increased physical fitness and restoration of certain biometric and biochemical parameters and blood pressure. PT also induced thermogenic modulations in skeletal muscle, WAT and BAT, and also improved the insulin signaling pathway. Collectively, PT was effective in treating MS by inducing improvement in physical fitness and interchangeable effects between skeletal muscle, WAT and BAT, suggesting a development of brown-like adipocyte cells

Swimming training induces liver adaptations to oxidative stress and insulin sensitivity in rats submitted to high-fat diet.

Oxidative stress, physical inactivity and high-fat (FAT) diets are associated with hepatic disorders such as metabolic syndrome (MS). The therapeutic effects of physical training (PT) were evaluated in rats with MS induced by FAT diet for 13 weeks, on oxidative stress and insulin signaling in the liver, during the last 6 weeks. FAT-sedentary (SED) rats increased body mass, retroperitoneal fat, mean arterial pressure (MAP) and heart rate (HR), and total cholesterol, serum alanine aminotransferase, glucose and insulin. Livers of FAT-SED rats increased superoxide dismutase activity, thiobarbituric acid-reactive substances, protein carbonyl and oxidized glutathione (GSSG); and decreased catalase activity, reduced glutathione/GSSG ratio, and the mRNA expression of insulin receptor substrate 1 (IRS-1) and serine/threonine kinase 2. FAT-PT rats improved in fitness and reduced their body mass, retroperitoneal fat, and glucose, insulin, total cholesterol, MAP and HR; and their livers increased superoxide dismutase and catalase activities, the reduced glutathione/GSSG ratio and the expression of peroxisome proliferator-activated receptor gamma and insulin receptor compared to FAT-SED rats. These findings indicated adaptive responses to PT by restoring the oxidative balance and insulin signaling in the liver and certain biometric and biochemical parameters as well as MAP in MS rats

Effect on cellular recruitment and the innate immune response by combining saponin, monophosphoryl lipid-A and incomplete freund?s adjuvant with Leishmania (Viannia) braziliensis antigens for a vaccine formulation.

The poor immunogenicity displayed by some antigens has encouraged the development of strategies to improve the immune response and safety of vaccine candidates, resulting in an intense search for substances that potentiate vaccine response. Adjuvants have these properties helping vaccine candidates to induce a strong, durable, and fast immune response. In this study, we evaluated the specific immune response of adjuvants alone, Saponin (SAP), Incomplete Freund?s Adjuvant (IFA) and Monophosphoryl lipid-A SE (MPL-SE ) and in combination with total antigen of L. braziliensis (LB): LBSAP, LBIFA and LBMPL. The specific immune response induced by these compositions demonstrated that they were powerfully immunogenic, increasing cellular infiltration in the skin. Draining lymph nodes cultures showed that LBIFA and LBMPL have higher ability to increase the capacity of APCs to present antigens, with increased frequency of CD11c+ CD86+ cells. SAP, MPL, LBSAP, LBIFA and LBMPL could activate lymphocytes increasing expression of CD69 and CD25. LBSAP group was an excellent inducer of pro-inflammatory cytokines at 24 h. At 48 h, higher cytokines production was observed in IFA, LBIFA, MPL and LBMPL groups. Our data demonstrate that LBSAP and LBMPL are potential formulations to be tested in other experimental models. Also, the data obtained could expand the knowledge about immune response after sensitization and also contribute to the development of safe, immunogenic and effective vaccines

Permanent Genetic Resources added to Molecular Ecology Resources Database 1 April 2013-31 May 2013

This article documents the addition of 234 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Acipenser sinensis, Aleochara bilineata, Aleochara bipustulata, Barbus meridionalis, Colossoma macropomum, Delia radicum, Drosophila nigrosparsa, Fontainea picrosperma, Helianthemum cinereum, Liomys pictus, Megabalanus azoricus, Pelteobagrus vachelli, Pleuragramma antarcticum, Podarcis hispanica type 1A, Sardinella brasiliensis and Sclerotinia homoeocarpa. These loci were cross-tested on the following species: Acipenser dabryanus, Barbus balcanicus, Barbus barbus, Barbus cyclolepis, Drosophila hydei, Drosophila melanogaster, Drosophila obscura, Drosophila subobscura, Fontainea australis, Fontainea fugax, Fontainea oraria, Fontainea rostrata, Fontainea venosa, Podarcis bocagei, Podarcis carbonelli, Podarcis liolepis, Podarcis muralis and Podarcis vaucheri

Permanent Genetic Resources added to Molecular Ecology Resources Database 1 April 2013-31 May 2013

This article documents the addition of 234 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Acipenser sinensis, Aleochara bilineata, Aleochara bipustulata, Barbus meridionalis, Colossoma macropomum, Delia radicum, Drosophila nigrosparsa, Fontainea picrosperma, Helianthemum cinereum, Liomys pictus, Megabalanus azoricus, Pelteobagrus vachelli, Pleuragramma antarcticum, Podarcis hispanica type 1A, Sardinella brasiliensis and Sclerotinia homoeocarpa. These loci were cross-tested on the following species: Acipenser dabryanus, Barbus balcanicus, Barbus barbus, Barbus cyclolepis, Drosophila hydei, Drosophila melanogaster, Drosophila obscura, Drosophila subobscura, Fontainea australis, Fontainea fugax, Fontainea oraria, Fontainea rostrata, Fontainea venosa, Podarcis bocagei, Podarcis carbonelli, Podarcis liolepis, Podarcis muralis and Podarcis vaucheri