Efeito da ingestão de extrato de chá verde rico em epigalocatequina-3-galato sobre reguladores metabólicos hepáticos de camundongos obesos induzidos por dieta hiperlipídica
Data
2015-04-30
Autores
Santamarina, Aline Boveto 
Orientadores
Oyama, Lila Missae
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: A esteatose hepática tem sido considerada a manifestação hepática da obesidade. Diversos estudos propõem efeitos benéficos das catequinas do chá verde, mas não está clara a influência da suplementação de extrato descafeinado de chá verde rico em EGCG no metabolismo hepático de lipídios. Objetivos: Avaliar o efeito da suplementação de EGCG sobre o metabolismo hepático de lipídios, na ativação da via LKB1 / AMPK nas alterações da homeostase energética que ocorrem na obesidade, em um modelo experimental de obesidade induzida por consumo prolongado de dieta hiperlipídica. Métodos: Os camundongos foram mantidos em gaiolas coletivas, divididos em quatro grupos: dieta controle + água ou EGCG; Dieta hiperlipídica + água ou EGCG. Todos os animais receberam água e dieta ad libitum durante 16 semanas. Os grupos de placebo receberam água (0,1 mL / dia) e grupos suplementados com EGCG (0,1 mL EGCG - 50mg / kg / dia) através de gavagem. Após eutanásia, porções de fígado (FIG), e sangue para obtenção de soro foram coletados. Avaliamos no soro perfil lipídico, glicose, insulina, adiponectina e AGL. Parte do FIG foi utilizado para análise histológica por HE, quantificação TAG, análise de citocinas pró e anti-inflamatórias, atividade enzimática dos complexos da cadeia respiratória mitocondrial, e análise da expressão proteica da via LKB1/AMPK, da via de sinalização da insulina e de receptores de citocinas. Resultados: A suplementação de EGCG se mostrou efetiva em reduzir o ganho de peso, em melhorar a sensibilidade à insulina, o perfil lipídico e a adiponectinemia. EGCG também se mostrou eficiente em estimular a expressão proteica de marcadores da via da insulina como AKT, IR e IRSI. Também estimulou a expressão proteica da via LKB1 / AMPK, aumentando SIRT1, LKB1, AMPK, que por consequência reduziram a expressão proteica de duas importantes enzimas lipogênicas, ACC e FAS, bem como dos fatores de transcrição SREBP 1-c e ChREBP envolvidos também na lipogênese. Adicionalmente EGCG se mostrou capaz de estimular atividade dos complexos enzimáticos da cadeia respiratória mitocondrial no fígado. Esse restabelecimento do perfil metabólico foi visível na análise histológica, pela ausência de acúmulo de gordura no fígado dos grupos suplementados com EGCG. Não houve modificação nos parâmetros inflamatórios avaliados. Conclusão: Este estudo demonstrou que o EGCG restaura o metabolismo hepático de lipídios, prevenindo NAFLD, demonstrando seu potencial como ferramenta na prevenção da obesidade.
Introduction: Hepatic steatosis has been considered the hepatic manifestation of obesity. Several studies suggest beneficial effects of green tea catechins, but it is not clear the influence on supplementation on decaffeinated green tea extract rich EGCG on hepatic metabolism of lipids. Aim: Assess the effect of EGCG supplementation on hepatic metabolism of lipids in the activation of the LKB1 / AMPK on changes in energy homeostasis that occur in obesity, in a experimental model induced by prolonged consumption of high-fat diet. Methods: Mice were kept in collective cages, divided into four groups: control diet + water or EGCG; high-fat diet + water or EGCG. All animals received water and food ad libitum for 16 weeks. The placebo group received water (0.1 mL / day) and groups supplemented with EGCG (0.1 mL EGCG - 50mg / kg / day) by gavage. The mice were euthanized and liver portions and blood, to obtain serum, were collected. We evaluated the serum lipid profile, blood glucose, insulin, adiponectin and NEFA. Liver was used for histological analysis by H & E, quantification of TAG, pro and anti-inflammatory cytokine analysis, the enzyme activity of the complexes of the mitochondrial respiratory chain. The hepatic tissue also was performed in analysis of protein expression of via LKB1 / AMPK, the insulin signaling pathway, and cytokine receptors. Results: The EGCG supplementation was effective in reducing weight gain, improving the insulin sensitivity, lipid profile and adiponectinemia. EGCG also proved effective in stimulating protein expression of insulin via markers as AKT, IR and IRS1. Also stimulated the protein expression on LKB1 / AMPK pathway, increasing SIRT1, LKB1, AMPK, which consequently reduced the protein expression of two important lipogenic enzymes, ACC and FAS as well as transcription factors SREBP-1 c and ChREBP also involved in lipogenesis . Additionally EGCG has been shown to stimulate the activity of the complexes on the mitochondrial respiratory chain in the liver. This restoration of the metabolic profile was visible in histological analysis, the absence of NAFLD in the groups supplemented with EGCG. There was no change in the assessed inflammatory parameters. Conclusion: This study showed that EGCG restores the hepatic metabolism of lipids, preventing fatty liver, demonstrating its potential as a tool in preventing obesity.
Introduction: Hepatic steatosis has been considered the hepatic manifestation of obesity. Several studies suggest beneficial effects of green tea catechins, but it is not clear the influence on supplementation on decaffeinated green tea extract rich EGCG on hepatic metabolism of lipids. Aim: Assess the effect of EGCG supplementation on hepatic metabolism of lipids in the activation of the LKB1 / AMPK on changes in energy homeostasis that occur in obesity, in a experimental model induced by prolonged consumption of high-fat diet. Methods: Mice were kept in collective cages, divided into four groups: control diet + water or EGCG; high-fat diet + water or EGCG. All animals received water and food ad libitum for 16 weeks. The placebo group received water (0.1 mL / day) and groups supplemented with EGCG (0.1 mL EGCG - 50mg / kg / day) by gavage. The mice were euthanized and liver portions and blood, to obtain serum, were collected. We evaluated the serum lipid profile, blood glucose, insulin, adiponectin and NEFA. Liver was used for histological analysis by H & E, quantification of TAG, pro and anti-inflammatory cytokine analysis, the enzyme activity of the complexes of the mitochondrial respiratory chain. The hepatic tissue also was performed in analysis of protein expression of via LKB1 / AMPK, the insulin signaling pathway, and cytokine receptors. Results: The EGCG supplementation was effective in reducing weight gain, improving the insulin sensitivity, lipid profile and adiponectinemia. EGCG also proved effective in stimulating protein expression of insulin via markers as AKT, IR and IRS1. Also stimulated the protein expression on LKB1 / AMPK pathway, increasing SIRT1, LKB1, AMPK, which consequently reduced the protein expression of two important lipogenic enzymes, ACC and FAS as well as transcription factors SREBP-1 c and ChREBP also involved in lipogenesis . Additionally EGCG has been shown to stimulate the activity of the complexes on the mitochondrial respiratory chain in the liver. This restoration of the metabolic profile was visible in histological analysis, the absence of NAFLD in the groups supplemented with EGCG. There was no change in the assessed inflammatory parameters. Conclusion: This study showed that EGCG restores the hepatic metabolism of lipids, preventing fatty liver, demonstrating its potential as a tool in preventing obesity.
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Citação
SANTAMARINA, Aline Boveto. Efeito da ingestão de extrato de chá verde rico em epigalocatequina-3-galato sobre reguladores metabólicos hepáticos de camundongos obesos induzidos por dieta hiperlipídica. 2015. 120 f. Dissertação (Mestrado em Nutrição) - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2015.