Effects of exercise type and intensity on visfatin and the metabolic syndrome in obesity / Efectos del tipo de ejercicio y de la intensidad en la visfatina y el síndrome metabólico en la obesidad / Efeitos do tipo de exercício e da intensidade na visfatina e a síndrome metabólica na obesidade

ABSTRACT Objective: Visfatin may regulate a variety of physiological functions and it has great potential to significantly enhance our knowledge of the treatment of metabolic syndrome. Metabolic syndrome (MS) refers to metabolic abnormalities, such as abdominal obesity, dyslipidemia, high low-density cholesterol, high blood pressure and diabetes, and physical activity is an important factor for the management of MS. Therefore, the purpose of this study is to investigate the effects of visfatin on MS and MS risk factors through differences in aerobic exercise intensity and exercise type based on the premise of the same amount of exercise (energy expenditure of 400 kcal per day). Method: Thirty two obese, middle-aged women were randomly assigned to exercise intensity groups VO2max 50% (MAE, n=8) and VO2max 80% (VAE, n=8) and to type of exercise groups VO2max 50% + TRX (MARE, n=8) and VO2max 80% + TRX (VARE, n=8). The exercise program was performed 5 times a week. The data was analyzed using two-way repeated measures ANOVA and post-hoc tests within groups with LSD. Results: Body weight (p<.01 and p<.001) and % body fat (p<.05 and p<.01) significantly decreased in all groups and visfatin only increased significantly after exercise in the VARE group (p<.05). TG, glucose, and waist circumstance (p<.05, p<.01, and p<.001) significantly decreased in all groups and HDL-C (p<.05) only increased significantly after exercise only in the MARE group. Conclusion: These results suggest that, in spite of differences in exercise intensity and exercise type, exercise is effective in improving obesity and MS risk factors, but further research is needed on the exact mechanisms of visfatin. Level of evidence I; Therapeutic Studies Investigating the Results of Treatment .

RESUMEN Objetivo: La visfatina puede regular diversas funciones fisiológicas y tiene gran potencial para mejorar significativamente nuestro conocimiento sobre el tratamiento del síndrome metabólico. El síndrome metabólico (SM) se refiere a anormalidades metabólicas, como obesidad abdominal, dislipidemia, colesterol de baja densidad elevado, hipertensión y diabetes, siendo la actividad física un factor importante para el manejo del SM. Siendo así, el objetivo de este estudio es investigar los efectos de la visfatina sobre los factores de riesgo de SM por medio de diferencias de la intensidad de ejercicios aeróbicos y del tipo de ejercicio, con base en la premisa de misma cantidad de ejercicio (gasto energético de 400 kcal por día). Método: Treinta y dos mujeres obesas de media edad fueron aleatoriamente designadas para grupos de intensidad de ejercicio con VO2máx de 50% (EAM, n = 8) y VO2máx de 80% (EAV, n = 8) y grupos con VO2máx de 50% + ERC (EARM, n = 8) y VO2máx de 80% + ERC (EARV, n = 8). El programa de ejercicios fue realizado cinco veces por semana. Los datos fueron analizados con ANOVA de dos vías con medidas repetidas y tests post-hoc en los grupos con DMS. Resultados: El peso corporal (p < 0,01 y p < 0,001) y porcentual de grasa corporal (p < 0,05 y p < 0,01) disminuyeron significativamente en todos los grupos y la visfatina sólo aumentó significativamente después del ejercicio en el grupo EARV (p < 0,05). Los triglicéridos, la glucosa y la circunferencia de la cintura (p < 0,05, p < 0,01 e p < 0,001) disminuyeron significativamente en todos los grupos y el HDL-C (p < 0,05) sólo aumentó significativamente después del ejercicio sólo en el grupo EARM. Conclusión: Esos resultados sugieren que, a pesar de las diferencias de intensidad y tipo de los ejercicios, los mismos son eficaces para mejorar la obesidad y los factores de riesgo del SM, por ende, son necesarias más investigaciones sobre los mecanismos exactos de la visfatina. Nivel de Evidencia I; Estudios terapéuticos - Investigación de los resultados del tratamiento .

RESUMO Objetivo: A visfatina pode regular diversas funções fisiológicas e tem grande potencial para aprimorar significativamente nosso conhecimento sobre o tratamento da síndrome metabólica. A síndrome metabólica (SM) refere-se a anormalidades metabólicas, como obesidade abdominal, dislipidemia, colesterol de baixa densidade elevado, hipertensão e diabetes, sendo a atividade física um fator importante para o manejo da SM. Assim sendo, o objetivo deste estudo é investigar os efeitos da visfatina sobre os fatores de risco de SM por meio de diferenças da intensidade de exercícios aeróbicos e do tipo de exercício, com base na premissa de mesma quantidade de exercício (gasto energético de 400 kcal por dia). Método: Trinta e duas mulheres obesas de meia-idade foram randomicamente designadas para grupos de intensidade de exercício com VO2máxde 50% (EAM, n = 8) e VO2máxde 80% (EAV, n = 8) e grupos com VO2máxde 50% + ERC (EARM, n = 8) e VO2máxde 80% + ERC (EARV, n = 8). O programa de exercícios foi realizado 5 vezes por semana. Os dados foram analisados com ANOVA de duas vias com medidas repetidas e testes post-hoc nos grupos com DMS. Resultados: O peso corporal (p < 0,01 e p < 0,001) e percentual de gordura corporal (p < 0,05 e p < 0,01) diminuíram significativamente em todos os grupos e a visfatina só aumentou significativamente depois do exercício no grupo EARV (p < 0,05). Triglicérides, glicose e circunferência da cintura (p < 0,05, p < 0,01 e p < 0,001) diminuíram significativamente em todos os grupos e o HDL-C (p < 0,05) só aumentou significativamente depois o exercício apenas no grupo EARM. Conclusão: Esses resultados sugerem que, apesar das diferenças de intensidade e tipo dos exercícios, eles são eficazes para melhorar a obesidade e os fatores de risco da SM, porém, são necessárias mais pesquisas sobre os mecanismos exatos da visfatina. Nível de Evidência I; Estudos terapêuticos - Investigação dos resultados do tratamento .

Dose-Response Relationship between Alanine Aminotransferase Levels within the Reference Interval and Metabolic Syndrome in Chinese Adults

PURPOSE: Elevation in serum alanine aminotransferase (ALT) levels is a biomarker for metabolic syndrome (MS); however, the relationship has not been fully investigated within the reference interval of ALT levels. Our objective was to explore the relationship between serum ALT levels within the reference interval and MS in Chinese adults. MATERIALS AND METHODS: This cross-sectional study included 16028 adults, who attended routine health check-ups at Shengli Oilfield Central Hospital from January 2006 to March 2012. The reference interval of serum ALT level was defined as less than 40 U/L. Logistic regression models and restricted cubic spline were used to evaluate the association of ALT with MS. RESULTS: The prevalence of MS in the total population was 13.7% (6.4% for females and 18.4% for males). Multiple logistic regression showed that ALT levels were positively associated with MS after adjustment for potential confounding factors. The odds ratio of MS in the top quartile was 4.830 [95% confidence interval (CI): 2.980–7.829] in females and 3.168 (95% CI: 2.649–3.790) in males, compared with the ALT levels in the bottom quartile. The restricted cubic spline models revealed a positive non-linear dose-response relationship between ALT levels and the risk of MS in women (p for nonlinearity was 0.0327), but a positive linear dose-response relationship in men (p for nonlinearity was 0.0659). CONCLUSION: Serum ALT levels within the reference interval are positively associated with MS in a dose-response manner. Elevated ALT levels, even within the reference interval, may reflect early dysmetabolic changes.

Role of GGT in diagnosis of metabolic syndrome : A clinic-based cross-sectional survey.

Background & objectives: The aim of this study is to know if the liver function tests (LFT), especially gamma glutamyl transferase (GGT), have a predictive value in diagnosis of metabolic syndrome (MS). Methods: A cross-sectional, single-center study was carried out with 908 subjects. Four hundred and forty two of these subjects were diagnosed with MS with IDF criteria; while other 466 were sex and age matched healthy control subjects. Blood pressure, liver function tests, fasting blood glucose levels and lipid profile of the subjects were recorded. Results: The mean values of alanine amino transferase (ALT), aspartate aminotransferase (AST) and GGT levels were statistically significantly higher in MS group. The mean values of liver enzymes, for female/ male subjects in MS group, AST; ALT and GGT respectively, were; 20.5/19.7 U/l; 25.9/28.5 U/l; 35.9/42.1 U/l. When the sample is divided into quartiles of the GGT levels, increase in GGT is positively correlated with increased MS prevalence. In ROC analysis GGT is as strongly associated with the IDF diagnostic components as is each individual IDF component, except elevated systolic blood pressure. In covariance analysis, there was significant relationship between elevated GGT levels and MS presence after adjustment for age, sex and MS diagnostic criteria; but not AST and ALT levels. In multivariance analysis, in MS group, a high GGT was positively associated with CVD prevalance (odds ratio: 2.011, 95% CI 1.10-4.57) compared to low GGT group independent of age, sex and smoking habits. Interpretation & conclusion: Elevated liver enzymes, although in normal ranges, especially at upper quartiles, play a central role in early diagnosis of fat overflow to the liver. Regarding the availability and simplicity of these tests in routine clinical practice, they, especially GGT, have potential to be considered in algorithms for metabolic syndrome.

Metformina e AMPK: um antigo fármaco e uma nova enzima no contexto da síndrome metabólica / Metformin and AMPK: an old drug and a new enzyme in the context of metabolic syndrome

A metformina é uma das drogas antidiabéticas orais mais prescritas mundialmente, entretanto seu mecanismo de ação permanece desconhecido. Os estudos do Diabetes Prevention Program Research Group demonstraram que tanto a administração de metformina como a mudança no estilo de vida (dieta e exercício físico) podem reduzir a incidência de diabetes melito tipo 2 (DM2). Uma possível conexão bioquímica entre essas duas terapias pode ser a proteína quinase ativada por AMP (AMPK). Essa enzima foi inicialmente descrita como um sensor energético celular, sendo ativada pelo exercício físico. Por outro lado, várias evidências experimentais indicam que a AMPK seja um alvo importante da ação da metformina. Este artigo discute as várias formas da regulação da AMPK, sugerindo um possível mecanismo para sua ativação pela metformina que envolve a formação de espécies reativas de nitrogênio. A ativação da AMPK determina ampla variedade de efeitos fisiológicos, incluindo o aumento da captação de glicose pelos músculos esqueléticos e aumento do catabolismo de lipídios, podendo ser interessante não apenas na prevenção e tratamento do DM2, mas também no contexto da síndrome metabólica. A descoberta da ativação da AMPK pela metformina faz dessa enzima importante alvo farmacológico.

Metformin is one of the most commonly prescribed oral antidiabetic agents worldwide. However, its mechanism of action remains unknown. The Diabetes Prevention Program Research Group studies have shown that metformin administration and lifestyle-intervention (diet and exercise) reduce the incidence of Diabetes Mellitus type 2 (DM2). A possible biochemical connection between both therapies may be the AMP-activated protein kinase (AMPK). This enzyme was originally described as a sensor of cellular energy status, being activated in exercise. On the other hand, several experimental evidences indicate that AMPK may be an important target of metformin action. This paper discusses various ways for AMPK regulation, suggesting a possible mechanism for its activation by metformin that involves the production of reactive nitrogen species. AMPK activation determines a wide variety of physiological effects, including enhanced glucose uptake by skeletal muscle and enhanced lipid catabolism. Thus, it may be a key player not only in the prevention and treatment of DM2, but also in the development of new treatments for obesity and the metabolic syndrome. The finding of AMPK activation by metformin draws attention to this enzyme as an important pharmacological target.

Adipose tissue expression of 11beta-Hydroxysteroid dehydrogenase type 1 in cushing's syndrome and in obesity

Glucocorticoids have a major role in determining adipose tissue metabolism and distribution. 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) is a NADPH-dependent enzyme highly expressed in the liver and adipose tissue. In most intact cells and tissues it functions as a reductase (to convert inactive cortisone to active cortisol). It has been hypothesized that tissue-specific deregulation of cortisol metabolism may be involved in the complex pathophysiology of the metabolic syndrome (MS) and obesity. Transgenic mice overexpressing 11betaHSD1 in adipose tissue develop obesity with all features of the MS, whereas 11betaHSD1-knockout mice are protected from both. The bulk of evidences points to an overexpression and increased activity of 11betaHSD1 also in human adipose tissue. However, 11betaHSD1 seems to adjust local cortisol concentrations independently of its plasma levels. In Cushing's syndrome, 11betaHSD1 is downregulated and may not be responsible for the abdominal fat depots; it also undergoes downregulation in response to weight loss in human obesity. The nonselective 11betaHSD1 inhibitor carbenoxolone improves insulin sensitivity in humans, and selective inhibitors enhance insulin action in diabetic mice liver, thereby lowering blood glucose. Thus, 11betaHSD1 is now emerging as a modulator of energy partitioning and a promising pharmacological target to treat the MS and diabetes.

Os glicocorticóides (GC) têm papel importante na determinação do metabolismo e da distribuição do tecido adiposo. A 11beta-hidroxisteróide desidrogenase tipo 1 (11betaHSD1) é uma enzima dependente de NADPH, altamente expressa nos tecidos hepático e adiposo. Em muitas células e tecidos intactos, ela funciona como redutase (convertendo cortisona em cortisol). Postula-se que uma desregulação tecido-específica do cortisol estaria envolvida na complexa fisiopatologia da síndrome metabólica (SM) e obesidade. Ratos que super-expressam 11betaHSD1 no tecido adiposo desenvolvem obesidade e todas as características da SM, enquanto ratos knockout para 11betaHSD1 são protegidos. Evidências apontam para uma super-expressão e aumento da atividade 11betaHSD1 também no tecido adiposo humano. Entretanto, a 11betaHSD1 parece ajustar a concentração local de cortisol independente da sua concentração sérica. Na síndrome de Cushing, a expressão da 11betaHSD1 é regulada para baixo, não devendo ser a causa dos depósitos de gordura visceral; em obesos, há também regulação para baixo em resposta à perda de peso. A carbenoxolona, um inibidor não seletivo da 11betaHSD1, melhora a sensibilidade insulínica em humanos e inibidores seletivos aumentam a sensibilidade insulínica hepática e melhoram o controle glicêmico em ratos diabéticos. Assim, a 11betaHSD1 está emergindo como um modulador da compartimentalização de energia e um alvo farmacológico promissor para o tratamento da SM e do diabetes.

Alteraciones de la tolerancia a la glucosa y frecuencia de síndrome metabólico en pacientes con enfermedad por hígado graso no alcohólico / Glucose tolerance alterations and frequency of metabolic syndrome among patients with non alcoholic fatty liver disease

Background: Non alcoholic fatty liver disease (NAFLD) is associated to diabetes mellitus, obesity, disturbances in serum lipid levels, insulin resistance and metabolic syndrome. Aim: To assess glucose tolerance and the presence of metabolic syndrome among patients with biopsy proven NAFLD. Patients and methods: Serum lipid levels, hepatic function tests were measured and an oral glucose tolerance test was performed in 46 patients (mean age 45±12 years, 36 females) without history of diabetes mellitus and with steatosis in a liver biopsy. Results: Mean body mass index of the sample was 37±12 kg/m². Seventeen percent had pure steatosis, 78 percent had steatohepatitis with or without fibrosis and 50 percent had fibrosis in the liver biopsy. Glucose intolerance and diabetes was found in 57 percent and 15 percent of cases, respectively. The presence of steatohepatitis was higher in diabetics, compared with subjects with glucose intolerance or a normal glucose response (43, 38 and 8 percent, respectively, p <0.0001). Ninety three percent had a metabolic syndrome and the proportion of biopsies with fibrosis was higher among subjects with more than three diagnostic criteria for metabolic syndrome compared with those with three or less criteria (59 and 46 percent, respectively, p <0.05). Conclusions: Glucose intolerance, diabetes and metabolic syndrome are common among patients with NAFLD, even when they are not obese.

Associação da gama-glutamil transferase e a síndrome metabólica em mulheres obesas / Association of gamma-glutamyl transferase and the metabolic syndrome in obese women

OBJETIVO: Avaliar a associação da gama-glutamil transferase (GGT) com a presença e número de co-morbidades da síndrome metabólica (SM). CASUíSTICA E MÉTODOS: Foram estudadas 353 mulheres consecutivamente admitidas num ambulatório de obesidade, com idade de 39,0 ± 11,4 anos e IMC de 41,3 ± 7,3kg/m². Todas as pacientes eram assintomáticas, não tinham história de ingestão excessiva de álcool ou de doença hepática. Pelo critério do National Cholesterol Education Program - Adult Treatment Panel III foi avaliada a presença de SM. RESULTADOS: A freqüência de SM nos pacientes foi de 50,7 por cento. A presença de GGT elevada foi maior nas pacientes com SM em relação às sem SM (32 por cento versus 20,7 por cento; p= 0,05). A média da GGT foi significativamente maior nas pacientes com SM do que naquelas sem SM (52,8 ± 42,3mg/dl; Md: 40,0 versus 40,1 ± 28,8mg/dl; Md: 33,0, p= 0,0001) e naquelas com cada co-morbidade isoladamente quando comparado às pacientes sem elas. Nas pacientes com associação de 3 co-morbidades da SM, a média de GGT foi 51,0 ± 39,2mg/dl (Md: 36,0), com 4 foi de 50,8 ± 50,4mg/dl (Md: 40,5) e com 5 foi de 64,8 ± 32,3mg/dl (Md: 61,0) (p= 0,0002). Houve correlação positiva entre glicose, triglicérides e pressão arterial sistólica e diastólica. CONCLUSÃO: Observou-se associação da GGT com a presença da SM ou de suas co-morbidades isoladamente em mulheres obesas.