RESUMO
Insulin resistance is the link between obesity and type 2 diabetes mellitus. The molecular mechanism by which obese individuals develop insulin resistance has not yet been fully elucidated; however, inconclusive and contradictory studies have shown that oxidative stress may be involved in the process. Thus, this study aimed to evaluate the effect of reactive species on the mechanism of insulin resistance in diet-induced obese mice. Obese insulin-resistant mice were treated with N-acetylcysteine (NAC; 50 mg/kg per day, for 15 days) by means of oral gavage. Twenty-four hours after the last NAC administration, the animals were euthanized and their tissues were extracted for biochemical and molecular analyses. NAC supplementation induced improved insulin resistance and fasting glycemia, without modifications in food intake, body weight, and adiposity. Obese mice showed increased dichlorofluorescein (DCF) oxidation, reduced catalase (CAT) activity, and reduced glutathione levels (GSH). However, treatment with NAC increased GSH and CAT activity and reduced DCF oxidation. The gastrocnemius muscle of obese mice showed an increase in nuclear factor kappa B (NFκB) and protein tyrosine phosphatase (PTP1B) levels, as well as c-Jun N-terminal kinase (JNK) phosphorylation compared to the control group; however, NAC treatment reversed these changes. Considering the molecules involved in insulin signaling, there was a reduction in insulin receptor substrate (IRS) and protein kinase B (Akt) phosphorylation. However, NAC administration increased IRS and Akt phosphorylation and IRS/PI3k (phosphoinositide 3-kinase) association. The results demonstrated that oxidative stress-associated obesity could be a mechanism involved in insulin resistance, at least in this animal model.
RESUMO
OBJECTIVE: To evaluate the effects of oxidative stress on insulin signaling in cardiac tissue of obese mice. METHODS: Thirty Swiss mice were equally divided (n=10) into three groups: Control Group, Obese Group, and Obese Group Treated with N-acetylcysteine. After obesity and insulin resistance were established, the obese mice were treated with N-acetylcysteine at a dose of 50mg/kg daily for 15 days via oral gavage. RESULTS: Higher blood glucose levels and nitrite and carbonyl contents, and lower protein levels of glutathione peroxidase and phosphorylated protein kinase B were observed in the obese group when compared with their respective control. On the other hand, treatment with N-acetylcysteine was effective in reducing blood glucose levels and nitrite and carbonyl contents, and significantly increased protein levels of glutathione peroxidase and phosphorylated protein kinase B compared to the Obese Group. CONCLUSION: Obesity and/or a high-lipid diet may result in oxidative stress and insulin resistance in the heart tissue of obese mice, and the use of N-acetylcysteine as a methodological and therapeutic strategy suggested there is a relation between them.
Assuntos
Acetilcisteína/farmacologia , Dieta Hiperlipídica , Sequestradores de Radicais Livres/farmacologia , Resistência à Insulina/fisiologia , Miocárdio/metabolismo , Obesidade/metabolismo , Estresse Oxidativo/fisiologia , Animais , Glicemia/análise , Western Blotting , Peso Corporal , Fluoresceínas/análise , Humanos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Carbonilação Proteica , Espécies Reativas de Oxigênio/análise , Valores de Referência , EspectrofotometriaRESUMO
OBJECTIVE: Insulin resistance-associated obesity and type 2 diabetes mellitus (T2DM) are commonly accompanied with metabolic lipid abnormalities and are characterized by hypertriglyceridemia and low HDL-c levels (atherogenic index plasma, AIP). The primary molecular mechanism that is known to cause insulin resistance is chronic low-grade inflammation. Considering that omega-3 fatty acid reduces subclinical inflammation, we hypothesized that fish oil could affect insulin resistance and AIP. Therefore, the present study evaluated the effects of fish oil supplementation on the inflammatory, insulin resistance, and atherogenic factors in overweight/obese T2DM patients. RESEARCH DESIGNS AND METHODS: In this study, we recruited 32 overweight and/or obese patients diagnosed with T2DM for over one year and who exhibited hypertriglyceridemia. These patients received fish oil supplementation (4.0â¯g/day) for eight weeks. Anthropometric and body composition measurements were obtained. In addition, blood samples were collected before and after omega-3 supplementation for the evaluation of lipid profile, glycemia, insulin, and inflammation. RESULTS: As expected, patients showed reduction in the TNFα, IL-1ß, and Il-6 levels after fish oil supplementation and showed improved insulin sensitivity (HOMA-IR) without observed alterations in anthropometric and body composition. These observations were followed by reduction in the levels of triglycerides and non-esterified fatty acids, increase in HDL cholesterol levels, and a significant reduction in triglycerides/HDL-c ratio, and total cholesterol/HDL-c ratio. CONCLUSION: Fish oil supplementation is effective in reducing the levels of proinflammatory cytokines, improving insulin resistance, and reducing atherogenic factors in overweight/obese and T2DM patients independent of weight loss.
Assuntos
Aterosclerose/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Óleos de Peixe/uso terapêutico , Inflamação/tratamento farmacológico , Resistência à Insulina , Sobrepeso/fisiopatologia , Adulto , Aterosclerose/fisiopatologia , Doença Crônica , Citocinas , Diabetes Mellitus Tipo 2/complicações , Ácidos Graxos Ômega-3/uso terapêutico , Feminino , Humanos , Hipertrigliceridemia/tratamento farmacológico , Hipertrigliceridemia/fisiopatologia , Inflamação/fisiopatologia , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/fisiopatologia , Sobrepeso/complicações , Projetos Piloto , Fatores de RiscoRESUMO
OBJECTIVE: To evaluate the effect of three types of muscular resistance training on adiposity, inflammation levels and insulin activity in Swiss mice with fat-rich diet-induced obesity. METHODS: Lean and obese male Swiss mice were selected and allocated to one of eight groups comprising eight mice each, as follows: standard diet + no training; standard diet + muscular resistance training; standard diet + hypertrophy training; standard diet + strength training; high-fat diet + no training; high-fat diet + muscular resistance training; high-fat diet + hypertrophy training; high-fat diet + strength training. The training protocol consisted of stair climbing for a 10-week period. Blood samples were collected for lactate analysis, glucose level measurement and insulin tolerance test. After euthanasia, adipose tissues were removed and weighed for adiposity index determination. Fragments of epididymal adipose tissue were then embedded for histological analysis or homogenized for tumor necrosis factor alpha level determination using the ELISA method. RESULTS: Ausency of differences in total training volume and blood lactate levels overall emphasize the similarity between the different resistance training protocols. Body weight loss, reduced adipocyte area and lower adiposity index were observed in trained obese mice, regardless of training modality. Different training protocols also improved insulin sensitivity and reduced inflammation levels. CONCLUSION: Resistance training protocols were equally effective in reducing body fat, inflammation levels and insulin resistance in obese mice.
Assuntos
Adiposidade/fisiologia , Hipertrofia/fisiopatologia , Inflamação/fisiopatologia , Resistência à Insulina/fisiologia , Exercícios de Alongamento Muscular/métodos , Obesidade/fisiopatologia , Condicionamento Físico Animal/fisiologia , Tecido Adiposo Branco/fisiopatologia , Animais , Glicemia/análise , Peso Corporal/fisiologia , Dieta Hiperlipídica , Ensaio de Imunoadsorção Enzimática , Masculino , Camundongos , Camundongos Obesos , Reprodutibilidade dos Testes , Treinamento Resistido/métodos , Fatores de Tempo , Fator de Necrose Tumoral alfa/análiseRESUMO
ABSTRACT Objective To evaluate the effect of three types of muscular resistance training on adiposity, inflammation levels and insulin activity in Swiss mice with fat-rich diet-induced obesity. Methods Lean and obese male Swiss mice were selected and allocated to one of eight groups comprising eight mice each, as follows: standard diet + no training; standard diet + muscular resistance training; standard diet + hypertrophy training; standard diet + strength training; high-fat diet + no training; high-fat diet + muscular resistance training; high-fat diet + hypertrophy training; high-fat diet + strength training. The training protocol consisted of stair climbing for a 10-week period. Blood samples were collected for lactate analysis, glucose level measurement and insulin tolerance test. After euthanasia, adipose tissues were removed and weighed for adiposity index determination. Fragments of epididymal adipose tissue were then embedded for histological analysis or homogenized for tumor necrosis factor alpha level determination using the ELISA method. Results Ausency of differences in total training volume and blood lactate levels overall emphasize the similarity between the different resistance training protocols. Body weight loss, reduced adipocyte area and lower adiposity index were observed in trained obese mice, regardless of training modality. Different training protocols also improved insulin sensitivity and reduced inflammation levels. Conclusion Resistance training protocols were equally effective in reducing body fat, inflammation levels and insulin resistance in obese mice.
RESUMO Objetivo Avaliar os efeitos de três tipos de treinamentos de resistência na adiposidade, na inflamação e na ação da insulina em camundongos Swiss obesos por dieta hiperlipídica. Métodos Camundongos Swiss machos magros e obesos foram selecionados e posteriormente separados em oito grupos com oito animais em cada: dieta padrão + não treinado; dieta padrão + treinamento de resistência muscular; dieta padrão + treinamento de hipertrofia; dieta padrão + treinamento de força; dieta hiperlipídica + não treinado; dieta hiperlipídica + treinamento de resistência muscular; dieta hiperlipídica + treinamento de hipertrofia; e dieta hiperlipídica + treinamento de força. O protocolo de treinamento consistiu em escaladas, por um período de 10 semanas. Amostras de sangue foram coletadas para análises de lactato, glicemia e teste de tolerância à insulina. Após eutanásia, os tecidos adiposos foram retirados e pesados para determinar o índice de adiposidade. Em seguida, parte do tecido adiposo epididimal foi emblocado para análises histológicas, e outra parte foi homogeneizada para análises de fator de necrose tumoral alfa por ELISA. Resultados O volume total de treinamento e a concentração sanguínea de lactato não diferiram entre os três treinos resistidos, sugerindo similaridade entre eles. Nos animais obesos, as três modalidades de treinamento reduziram o peso corporal, a área adipocitária e o índice de adiposidade. Os três tipos de treinamentos ainda melhoraram a tolerância à insulina e reduziram a inflamação. Conclusão Os protocolos de treinamento resistido foram igualmente efetivos em reduzir a adiposidade, a inflamação e a resistência à ação da insulina em camundongos obesos.
Assuntos
Animais , Masculino , Camundongos , Condicionamento Físico Animal/fisiologia , Resistência à Insulina/fisiologia , Adiposidade/fisiologia , Exercícios de Alongamento Muscular/métodos , Hipertrofia/fisiopatologia , Inflamação/fisiopatologia , Obesidade/fisiopatologia , Fatores de Tempo , Glicemia/análise , Peso Corporal/fisiologia , Ensaio de Imunoadsorção Enzimática , Reprodutibilidade dos Testes , Fator de Necrose Tumoral alfa/análise , Tecido Adiposo Branco/fisiopatologia , Treinamento Resistido/métodos , Dieta Hiperlipídica , Camundongos , Camundongos ObesosRESUMO
ABSTRACT Objective To evaluate the effects of oxidative stress on insulin signaling in cardiac tissue of obese mice. Methods Thirty Swiss mice were equally divided (n=10) into three groups: Control Group, Obese Group, and Obese Group Treated with N-acetylcysteine. After obesity and insulin resistance were established, the obese mice were treated with N-acetylcysteine at a dose of 50mg/kg daily for 15 days via oral gavage. Results Higher blood glucose levels and nitrite and carbonyl contents, and lower protein levels of glutathione peroxidase and phosphorylated protein kinase B were observed in the obese group when compared with their respective control. On the other hand, treatment with N-acetylcysteine was effective in reducing blood glucose levels and nitrite and carbonyl contents, and significantly increased protein levels of glutathione peroxidase and phosphorylated protein kinase B compared to the Obese Group. Conclusion Obesity and/or a high-lipid diet may result in oxidative stress and insulin resistance in the heart tissue of obese mice, and the use of N-acetylcysteine as a methodological and therapeutic strategy suggested there is a relation between them.
RESUMO Objetivo Avaliar os efeitos do estresse oxidativo sobre a sinalização da insulina em tecido cardíaco de camundongos obesos. Métodos Utilizaram-se 30 camundongos Swiss subdivididos igualmente (n=10) em três grupos: Grupo Controle, Grupo Obeso e Grupo Obeso Tratado com N-acetilcisteína. Após estabelecidas a obesidade e a resistência à insulina, os camundongos obesos foram tratados diariamente, durante 15 dias, via gavagem oral, com N-acetilcisteína na dose de 50mg/kg. Resultados Observaram-se maiores níveis de glicose sanguínea, conteúdos de nitrito e carbonil, e menores níveis proteicos de glutationa peroxidase e proteína quinase B fosforilada no Grupo Obeso quando comparado a seu respectivo controle. Por outro lado, o tratamento com N-acetilcisteína se mostrou eficiente em diminuir os níveis glicêmicos, os conteúdos de nitrito e carbonil, e aumentar significativamente os níveis proteicos de glutationa peroxidase e proteína quinase B fosforilada, quando comparados ao Grupo Obeso. Conclusão Obesidade e/ou dieta hiperlipídica levam a estresse oxidativo e à resistência à insulina no tecido cardíaco de camundongos obesos, e o uso da N-acetilcisteína como estratégia metodológica e terapêutica sugeriu haver relação entre ambos.
Assuntos
Humanos , Animais , Masculino , Camundongos , Acetilcisteína/farmacologia , Resistência à Insulina/fisiologia , Sequestradores de Radicais Livres/farmacologia , Estresse Oxidativo/fisiologia , Dieta Hiperlipídica , Miocárdio/metabolismo , Valores de Referência , Espectrofotometria , Glicemia/análise , Peso Corporal , Western Blotting , Espécies Reativas de Oxigênio/análise , Estresse Oxidativo/efeitos dos fármacos , Carbonilação Proteica , Fluoresceínas/análiseRESUMO
OBJECTIVE: To evaluate the effects of resveratrol on insulin signaling and inflammation pathway in the myocardium of high-fat diet-induced obese rats. METHODS: Thirty Wistar rats were divided into a control group (n=10, standard diet), obese group (n=10, high-fat diet), and obese supplemented with resveratrol group (n=10, 20 mg/kg/day) for eight weeks. An insulin tolerance test was performed at the end of the study period "0" (without insulin), 5, 10, 15, 20, 25, and 30 minutes after an intraperitoneal injection of insulin (2 U/kg). Body and epididymal adipose tissue were weighed. Fragments of the myocardium were extracted for Western blot analyses of insulin pathway and proinflammatory molecules. RESULTS: Resveratrol increased the rate of glucose disappearance, phosphorylation of the insulin receptor, insulin receptor substrate 1, and protein kinase B; and reduced expression of tumor necrosis factor alpha and of the molecules involved in proinflammatory signal transduction, namely Ikappa B kinase and nuclear factor kappa B complex. The results also suggest that higher insulin sensitivity and lower levels of proinflammatory molecules occurred regardless of weight and epididymal adipose tissue loss. CONCLUSION: Resveratrol increases insulin action and reduces inflammatory molecules in the myocardium. .
OBJETIVO: Avaliar o efeito do resveratrol sobre a via de sinalização da insulina e melhora do quadro inflamatório no miocárdio de ratos Wistar obesos induzidos por dieta. MÉTODOS: Ratos Wistar foram divididos em grupos: controle (dieta padrão para roedores), obeso (dieta hiperlipídica) e obeso suplementado com resveratrol (20 mg/kg/dia), por 8 semanas (n=10). Ao final do período experimental, realizou-se o teste de tolerância à insulina, nos tempos 0 (sem insulina), 5, 10, 15, 20, 25 e 30 minutos após injeção intraperitoneal de insulina (2 U/kg). O peso corporal e o tecido adiposo epididimal foram mensurados. Fragmentos do miocárdio foram extraídos para análises da via da insulina e moléculas pró-inflamatórias através de Western blot. RESULTADOS: Os resultados indicam que a intervenção com resveratrol aumenta a constante de decaimento da glicose, fosforilação do receptor de insulina, substrato do receptor de insulina e da proteína quinase B. A suplementação de resveratrol também reduziu os níveis proteicos do fator de necrose tumoral alfa e de moléculas envolvidas com a transdução do sinal pró-inflamatório (quinase indutora do kappa B e fator nuclear kappa B). Os resultados ainda sugerem que a melhora na sensibilidade à insulina e a redução das moléculas pró-inflamatórias ocorreram independentemente da perda de peso corporal e da redução do tecido adiposo epididimal. CONCLUSÃO: A suplementação de resveratrol aumenta a sensibilidade à insulina, o que está relacionado à redução de fatores inflamatórios no miocárdio. .