Influência do polimorfismo no gene LEPR no estado de hiperleptinemia e na resposta ao tratamento interdisciplinar para mudança do estilo de vida
Data
2015-05-31
Autores
Corgosinho, Flávia Campos 
Orientadores
Dâmaso, Ana Raimunda
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: Embora a obesidade esteja associada a alterações metabólicas e aumento do risco cardiovascular, nem todos os indivíduos obesos apresentam essas anormalidades. Do mesmo modo, nem todos obesos respondem de forma semelhante após tratamento para o emagrecimento, o que pode ser parcialmente explicado por variações genéticas. Objetivo: Investigar a prevalência do polimorfismo de nucleotídeo único no gene do receptor da leptina LEPR (rs2767485) e sua influência na resposta de uma intervenção interdisciplinar em adolescentes obesos. Métodos: Um total de 81 (oitenta e um) adolescentes obesos foi inscrito em um ano de terapia interdisciplinar. Amostras de sangue foram coletadas para análises metabólicas, dosagem de adipocinas, neuropeptídeos e para genotipagem. A gordura visceral foi mensurada por ultrassom e composição corporal foi medida por pletismografia. Os adolescentes foram agrupados de acordo com o genótipo (grupo TT ou CT + CC). Os testes estatísticos foram feitos de acordo com a normalidade, sendo o valor de p fixado em <0,05. Resultados: Dos 81 adolescentes que iniciaram a terapia, 76 permaneceram até o final. As distribuições do genótipo foram: TT = 49%; CT = 41%; CC = 10%. No início do estudo, o grupo CT + CC apresentou maiores valores de VLDL-c, triglicérides e níveis de MCP-1, quando comparados com o grupo TT. No grupo TT houve melhor resposta da terapia em todos os parâmetros: apresentaram maior redução no IMC, melhor resposta no perfil lipídico e maior redução na prevalência de hiperleptinemia, quando comparados com o grupo CT + CC. O modelo de regressão linear mostrou que a razão lep/adipo é um fator independente para alterações nos triglicerídeos e no VLD-L no grupo CT + CC. Conclusão: A variação genética no LEPR (rs2767485) pode aumentar as chances para o desenvolvimento de doenças cardiovasculares em adolescentes obesos por aumentar os triglicerídeos, VLDL-c e MCP-1, além de prejudicar a melhora desses parâmetros. Os dados sugerem que o genótipo CT + CC, apresenta maior dificuldade em normalizar a via neuroendócrina do balanço energético e o estado de hiperleptinemia.
Background: Although obesity is associated with metabolic alterations and increased cardiovascular risk, not all obese subjects have these abnormalities. Indeed, not everyone respond in the same way to obesity treatment, which could be partly explained by genetic variations. Aim: To investigate the influence of single nucleotide polymorphisms in the leptin receptor gene LEPR (rs2767485) on cardiovascular risk after a multifaceted 1-year weight loss therapy among obese Brazilian adolescents. Methods: A total of 81 obese adolescents were enrolled in one year of interdisciplinary weight loss therapy. Blood samples were collected to analyse metabolic, adipokines, neuropeptides parameters and genetic variation on Leptin receptor gene (rs2767485). Visceral fat was measured by ultrasound and body composition was measured by pletismography. Adolescents were grouped according to genotype (TT or CT+CC group). Statistical analyses was performed according to normality, with p value was set at < 0.05. Resuts: Seventy-six adolescents completed the therapy. Genotypes distribution were: TT = 49%; CT = 41%; CC = 10%. At baseline CT+CC group pressented higher levels of VLDL-c, triglycerides and MCP-1, when compared with TT group. It was observed better response to the therapy on TT group. They had better delta of BMI, improved significant lipid profile and greater reduction on hyperleptinemia state, when compared with CT+CC group.The linear regression model showed that lep/adipo ratio was an independent predictor for VLDL and triglycerides on CT+CC group. Conclusion: Genetic variation on LEPR (rs2767485) might increases the cardiovascular risk in obese adolescents, by increasing triglycerides, VLDL and MCP-1. Moreover, data suggest that CT+CC group presents more difficult on reducing hyperleptinemic state and neuroendocrine pathways.
Background: Although obesity is associated with metabolic alterations and increased cardiovascular risk, not all obese subjects have these abnormalities. Indeed, not everyone respond in the same way to obesity treatment, which could be partly explained by genetic variations. Aim: To investigate the influence of single nucleotide polymorphisms in the leptin receptor gene LEPR (rs2767485) on cardiovascular risk after a multifaceted 1-year weight loss therapy among obese Brazilian adolescents. Methods: A total of 81 obese adolescents were enrolled in one year of interdisciplinary weight loss therapy. Blood samples were collected to analyse metabolic, adipokines, neuropeptides parameters and genetic variation on Leptin receptor gene (rs2767485). Visceral fat was measured by ultrasound and body composition was measured by pletismography. Adolescents were grouped according to genotype (TT or CT+CC group). Statistical analyses was performed according to normality, with p value was set at < 0.05. Resuts: Seventy-six adolescents completed the therapy. Genotypes distribution were: TT = 49%; CT = 41%; CC = 10%. At baseline CT+CC group pressented higher levels of VLDL-c, triglycerides and MCP-1, when compared with TT group. It was observed better response to the therapy on TT group. They had better delta of BMI, improved significant lipid profile and greater reduction on hyperleptinemia state, when compared with CT+CC group.The linear regression model showed that lep/adipo ratio was an independent predictor for VLDL and triglycerides on CT+CC group. Conclusion: Genetic variation on LEPR (rs2767485) might increases the cardiovascular risk in obese adolescents, by increasing triglycerides, VLDL and MCP-1. Moreover, data suggest that CT+CC group presents more difficult on reducing hyperleptinemic state and neuroendocrine pathways.
Descrição
Citação
CORGOSINHO, Flávia Campos. Influência do polimorfismo no gene LEPR no estado de hiperleptinemia e na resposta ao tratamento interdisciplinar para mudança do estilo de vida. 2015. 122 f. Tese (Doutorado em Nutrição) - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2015.