Muscle protein metabolism in neonatal alloxan-administered rats: effects of continuous and intermittent swimming training

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Role of PKC and CaV1.2 in Detrusor Overactivity in a Model of Obesity Associated with Insulin Resistance in Mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Transportadores de glicose na síndrome metabólica

A regulação da homeostasia intra e extra-celular da glicose está diretamente relacionada ao controle preciso da expressão dos genes que codificam as diferentes isoformas de proteínas transportadoras de glicose, as quais se expressam de maneira tecido-específica, em conseqüência do padrão de ativação dos fatores transcricionais reguladores de cada gene, em cada tipo celular. A síndrome metabólica (SM) abrange uma grande variedade de alterações fisiopatológicas, todas de repercussões sistêmicas, acometendo os mais distintos territórios do organismo, nos quais alterações nos transportadores de glicose presentes são observadas em maior ou menor grau. A presente revisão abordará as alterações na expressão de transportadores de glicose claramente demonstradas na literatura, cujas repercussões nos fluxos territoriais de glicose auxiliam na compreensão de mecanismos fisiopatológicos da SM, assim como dos tratamentos propostos para esta entidade.

A Hypercaloric pellet-diet cycle induces obesity and co-morbidities in wistar rats

O objetivo do estudo foi desenvolver um ciclo de dietas hipercalóricas para promover obesidade em ratos. Ratos Wistar foram distribuídos em dois grupos: dieta normal (ND = 32; 3,5 kcal/g) e dietas hipercalóricas (HD; n = 32; 4,6 kcal/g). O grupo ND recebeu ração comercial e os animais HD um ciclo de diferentes dietas hipercalóricas, por 14 semanas. As variáveis analisadas foram peso corporal, parâmetros metabólicos e hormonais, pressão arterial sistólica e teste oral de tolerância à glicose. O nível de significância foi de 5%. O ciclo de dietas hipercalóricas promoveu aumento de peso e gordura corporal, pressão arterial sistólica e níveis séricos de glicose, triacilglicerol, insulina e leptina no grupo HD. Além disso, o grupo HD apresentou tolerância à glicose diminuída. em conclusão, os resultados deste estudo mostram que o ciclo de dietas hipercalóricas promove obesidade e exibe várias características comumente associadas com a obesidade humana, como aumento da pressão arterial, resistência à insulina, hiperglicemia, hiperinsulinemia, hiperleptinemia e dislipidemia.

Consumo de frutas, verduras e legumes associado à Síndrome Metabólica e seus componentes em amostra populacional adulta

A síndrome metabólica (SM) aumenta o risco de eventos cardiovasculares e o consumo adequado de frutas, verduras e legumes (FVL) está relacionado a sua prevenção. Objetivo: Identificar o consumo de FVL e sua relação com a SM e seus componentes em amostra populacional adulta. Estudo prospectivo de corte transversal com 636 indivíduos adultos, no período de 2004 a 2008. Foram realizadas avaliações antropométrica, clínica, dietética e bioquímica com todos participantes. A SM foi classificada pelo NCEP ATP-III, modificada para a glicose >100mg/dl. A regressão logística foi utilizada para verificar a razão de chance entre o consumo de FVL com a SM e seus componentes, e o nível de significância adotado foi de 5%. O consumo de frutas adequado se mostrou protetor para obesidade abdominal (OR: 0,77; IC: 0,38-0,93), hipertrigliceridemia (OR: 0,76; IC: 0,35-0,96) e presença de SM (OR: 0,78; IC: 0,39-0,96), e o consumo adequado de FVL apresentou efeito protetor para a presença de SM (OR: 0,79; IC: 0,41-0,95). A análise isolada do consumo adequado de verduras e legumes não mostrou efeitos de proteção/risco para a presença de SM e de seus componentes. O consumo adequado de FVL apresentou efeito protetor para a presença de SM e o consumo adequado de frutas exerceu efeito protetor tanto para a presença de SM e como de seus componentes.

Long-term nutrition education reduces several risk factors for type 2 diabetes mellitus in Brazilians with impaired glucose tolerance

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Chronic consumption of fructose rich soft drinks alters tissue lipids of rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The effectiveness of educational practice in diabetic foot: a view from Brazil

Background: The aim of the present study was to evaluate the prevention and self-inspection behavior of diabetic subjects with foot at ulcer risk, no previous episode, who participated in the routine visits and standardized education provided by the service and who received prescribed footwear. This evaluation was carried out using a questionnaire scoring from 0-10 (high scores reflect worse practice compliance).Results: 60 patients were studied (30 of each sex); mean age was 62 years, mean duration of the disease was 17 years. As for compliance, 90% showed a total score <= 5, only 8.7% regularly wore the footwear supplied; self foot inspection 65%, 28,3% with additional familiar inspection; creaming 77%; proper washing and drying 88%; proper cutting of toe nails 83%; no cuticle cutting 83%; routine shoe inspection 77%; no use of pumice stones or similar abrasive 70%; no barefoot walking 95%.Conclusion: the planned and multidisciplinary educational approach enabled high compliance of the ulcer prevention care needed in diabetic patients at risk for complications. In contrast, compliance observed for the use of footwear provided was extremely low, demonstrating that the issue of its acceptability should be further and carefully addressed. In countries of such vast dimensions as Brazil multidisciplinary educational approaches can and should be performed by the services providing care for patients with foot at risk for complications according to the reality of local scenarios. Furthermore, every educational program should assess the learning, results obtained and efficacy in the target population by use of an adequate evaluation system.

Autoimmunity does not contribute to the highly prevalent glucose metabolism disturbances in a Japanese Brazilian population

The Japanese Brazilian population has one of the highest prevalences of diabetes worldwide. Despite being non-obese according to standard definitions, their body fat distribution is typically central. We investigated whether a subset of these subjects had autoantibodies that would suggest a slowly progressive form of type 1 diabetes. A total of 721 Japanese Brazilians (386 men) in the 30- to 60-year age group underwent clinical examination and laboratory procedures, including a 75-g oral glucose tolerance test and determinations of serum autoantibodies. Antibodies to glutamic acid decarboxylase (GADab) were determined by radioimmunoassay and to thyroglobulin (TGab) and thyroperoxidase (TPOab) by flow-cytometry assays. Mean body mass index was 25.2 ± 3.8 kg/m2, but waist circumference was elevated according to the Asian standards. Diabetes, impaired glucose tolerance, and impaired fasting glycemia were found in 31%, 22%, and 22%, respectively, and 53% of the subjects had metabolic syndrome. Glutamic acid decarboxylase (GADab) was positive in 4.72%, TGab in 9.6%, and TPOab in 10% of the whole sample. When participants were stratified according to the presence of thyroid antibodies, similar frequencies of GADab were found in positive and negative groups. The prevalence rates of glucose metabolism disturbances did not differ between GADab positive and negative groups. Our data did not support the view that autoimmune injury could contribute to the high prevalence of diabetes seen in Japanese Brazilians, and the presence of co-morbidities included in the spectrum of metabolic syndrome favors the classification as type 2 diabetes.

Diet-induced obesity impairs AKT signalling in the retina and causes retinal degeneration

Retinopathy, a common complication of diabetes, is characterized by an unbalanced production of nitric oxide (NO), a process regulated by nitric oxide synthase (NOS). We hypothesized that retinopathy might stem from changes in the insulin receptor substrate (IRS)/PI3K/AKT pathway and/or expression of NOS isoforms. Thus, we analysed the morphology and apoptosis index in retinas of obese rats in whom insulin resistance had been induced by a high-fat diet (HFD). Immunoblotting analysis revealed that the retinal tissue of HFD rats had lower levels of AKT1, eNOS and nNOS protein than those of samples taken from control animals. Furthermore, immunohistochemical analyses indicated higher levels of iNOS and 4-hydroxynonenal and a larger number of apoptotic nuclei in HFD rats. Finally, both the inner and outer retinal layers of HFD rats were thinner than those in their control counterparts. When considered alongside previous results, these patterns suggest two major ways in which HFD might impact animals: direct activity of ingested fatty acids and/or via insulin-resistance-induced changes in intracellular pathways. We discuss these possibilities in further detail and advocate the use of this animal model for further understanding relationships between retinopathy, metabolic syndrome and type 2 diabetes. © 2012 John Wiley & Sons, Ltd.

Dietary, anthropometric, and biochemical determinants of uric acid in free-living adults

Background: High plasma uric acid (UA) is a prerequisite for gout and is also associated with the metabolic syndrome and its components and consequently risk factors for cardiovascular diseases. Hence, the management of UA serum concentrations would be essential for the treatment and/or prevention of human diseases and, to that end, it is necessary to know what the main factors that control the uricemia increase. The aim of this study was to evaluate the main factors associated with higher uricemia values analyzing diet, body composition and biochemical markers. Methods. 415 both gender individuals aged 21 to 82 years who participated in a lifestyle modification project were studied. Anthropometric evaluation consisted of weight and height measurements with later BMI estimation. Waist circumference was also measured. The muscle mass (Muscle Mass Index - MMI) and fat percentage were measured by bioimpedance. Dietary intake was estimated by 24-hour recalls with later quantification of the servings on the Brazilian food pyramid and the Healthy Eating Index. Uric acid, glucose, triglycerides (TG), total cholesterol, urea, creatinine, gamma-GT, albumin and calcium and HDL-c were quantified in serum by the dry-chemistry method. LDL-c was estimated by the Friedewald equation and ultrasensitive C-reactive protein (CRP) by the immunochemiluminiscence method. Statistical analysis was performed by the SAS software package, version 9.1. Linear regression (odds ratio) was performed with a 95% confidence interval (CI) in order to observe the odds ratio for presenting UA above the last quartile (♂UA > 6.5 mg/dL and ♀ UA > 5 mg/dL). The level of significance adopted was lower than 5%. Results: Individuals with BMI ≥ 25 kg/m§ssup§2§esup§ OR = 2.28(1.13-4.6) and lower MMI OR = 13.4 (5.21-34.56) showed greater chances of high UA levels even after all adjustments (gender, age, CRP, gamma-gt, LDL, creatinine, urea, albumin, HDL-c, TG, arterial hypertension and glucose). As regards biochemical markers, higher triglycerides OR = 2.76 (1.55-4.90), US-CRP OR = 2.77 (1.07-7.21) and urea OR = 2.53 (1.19-5.41) were associated with greater chances of high UA (adjusted for gender, age, BMI, waist circumference, MMI, glomerular filtration rate, and MS). No association was found between diet and UA. Conclusions: The main factors associated with UA increase were altered BMI (overweight and obesity), muscle hypotrophy (MMI), higher levels of urea, triglycerides, and CRP. No dietary components were found among uricemia predictors. © 2013 de Oliveira et al.; licensee BioMed Central Ltd.

Infliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats

High systolic blood pressure caused by endothelial dysfunction is a comorbidity of metabolic syndrome that is mediated by local inflammatory signals. Insulin-induced vasorelaxation due to endothelial nitric oxide synthase (eNOS) activation is highly dependent on the activation of the upstream insulin-stimulated serine/threonine kinase (AKT) and is severely impaired in obese, hypertensive rodents and humans. Neutralisation of circulating tumor necrosis factor-α (TNFα) with infliximab improves glucose homeostasis, but the consequences of this pharmacological strategy on systolic blood pressure and eNOS activation are unknown. To address this issue, we assessed the temporal changes in the systolic pressure of spontaneously hypertensive rats (SHR) treated with infliximab. We also assessed the activation of critical proteins that mediate insulin activity and TNFα-mediated insulin resistance in the aorta and cardiac left ventricle. Our data demonstrate that infliximab prevents the upregulation of both systolic pressure and left ventricle hypertrophy in SHR. These effects paralleled an increase in AKT/eNOS phosphorylation and a reduction in the phosphorylation of inhibitor of nuclear factor-κB (Iκβ) and c-Jun N-terminal kinase (JNK) in the aorta. Overall, our study revealed the cardiovascular benefits of infliximab in SHR. In addition, the present findings further suggested that the reduction of systolic pressure and left ventricle hypertrophy by infliximab are secondary effects to the reduction of endothelial inflammation and the recovery of AKT/eNOS pathway activation. © 2012 Elsevier B.V.

Pathological and behavioral risk factors for higher serum c-reactive protein concentrations in free-living adults - A Brazilian community-based study

Low-grade chronic systemic inflammation is often associated with chronic non-communicable diseases, and its most frequently used marker, the C-reactive protein (CRP), has become an identifier of such diseases as well as an independent predictor for cardiovascular disorders and mortality. CRP is produced in response to pro-inflammatory signaling and to individual and behavioral factors, leading to pathological states. The aim of this study was to rank the predicting factors of high CRP concentrations in free-living adults from a community-based sample. We evaluated 522 adults (40-84 years old; 381 women) for anthropometric characteristics, dietary intake, clinical and physical tests, and blood analysis. Subjects were assigned to groups, according to CRP concentrations, as normal CRP (G1;<3.0 mg/L; n = 269), high CRP (G2; 3.0-6.0 mg/L; n = 139), and very high CRP (G3; >6.0 mg/dL; n = 116). Statistical comparison between groups used one-way ANOVA or Kruskal-Wallis tests, and prediction of altered values in increasing CRP was evaluated by proportional hazard models (odds ratio). CRP distribution was influenced by gender, body mass index, body and abdominal fatness, blood leukocytes, and neutrophil counts. The higher CRP group was discriminated by the above variables in addition to lower VO2max, serum metabolic syndrome components (triglycerides, glucose, and HDL cholesterol), higher insulin, homeostasis assessment of insulin resistance, uric acid, gamma-GT, and homocysteine. After adjustments, only fatness, blood leukocytes, and hyperglycemia remained as independent predictors for increased serum CRP concentrations. Intervention procedures to treat low-grade chronic inflammation in overweight women would mainly focus on restoring muscle mass and functions in addition to an antioxidant-rich diet. © 2012 Springer Science+Business Media, LLC.

Manifestações clínicas, bioquímicas, ultrassonográficas e metabólicas da síndrome dos ovários policísticos em adolescentes

PURPOSE: To evaluate the clinical, ultrasonographic, biochemical and metabolic alterations of adolescents with polycystic ovary syndrome (PCOS). METHODS: Retrospective observational study conducted on 44 adolescents aged 12 to 19 years, diagnosed with PCOS according to the Rotterdam Consensus. Metabolic changes were assessed according to the recommendations of the International Diabetes Federation, considering: waist circumference (WC) ≥90th percentile (10-15 years of age) or >80 cm (age >16 years), fasting glucose >100 mg/dL, triglycerides >150 mg/dL, HDL <40 mg/dL, and blood pressure ≥Hg 130/85 mm. RESULTS: Mean age was 16.7±2.2 years and age at menarche was 11.8±1.4 years. The menstrual irregularity most frequently observed was amenorrhea (72.7%) followed by oligomenorrhea (27.3%); hirsutism was observed in 86.4% and acne in 56.8%. Polycystic ovaries were observed by ultrasound only in 27.3%. Mean BMI was 30.3±6.6 kg/m2. According to BMI, 52.3% of adolescents were obese, 13.6% were overweight and 6.8% had a healthy weight. Increased waist circumference (63.6%, 28/44) and the reduction of HDL-C (34.1%, 15/44) were the metabolic changes most frequently observed. Increased triglycerides were observed in 27.3% (12/44) and increased blood pressure and impaired fasting glucose were found in 9.1% (4/44) and 4.5% (2/44) of cases, respectively. Acanthosis nigricans was observed in 52.3% and insulin resistance in 62.8% of the adolescents with PCOS. Metabolic syndrome was identified in six children (13.6%), all of them obese or overweight. CONCLUSION: In the adolescents with PCOS studied here, menstrual irregularity and hirsutism were the most common clinical manifestations, while the sonographic findings consistent with polycystic ovaries were less prevalent. Obesity associated with insulin resistance predisposes these adolescents to a higher frequency of metabolic disorders.

Energy and fat intake are not associated with abdominal adiposity

Background and objective: Central or abdominal obesity (AA) is a highly prevalent determinant of the metabolic syndrome and its control requires intervention strategies. This study investigated the risk factors associated with the presence of AA in hospitalized individuals. Patients and methods: A total of 1626patients were studied. The investigated risk factors possibly associated with AA were gender, age, body mass index (BMI), habitual energy intake (HEI) and fat intake (FI). AA was determined by waist circumference (WC) and waist-to-hip ratio (WHR). The chi2, Mann-Whitney and Kruskal-Wallis tests were used to compare the data and univariate and multiple logistic regressions were used to identify the predictive factors of AA. Results: Women were at higher risk of developing AA than men (P. <. 0.0001). The HEI and FI of individuals with and without AA and of women and men were not significantly different. According to multivariate analysis, HEI was not a predictive factor of AA, contrary to gender and age. The risk factors for AA, determined by WC, were gender (OR. = 6.8; CI. = 5.3-8.7) and age (OR. = 1.0; CI. = 1.0-1.0). Women were six times more likely to develop AA than men. Conclusions: Evidence of an association between AA and HEI or FI was not found, but gender and age were associated with AA. © 2013 Elsevier Masson SAS.