Relação entre a ingestão de micronutrientes e alterações citogenéticas e genômicas na obesidade mórbida
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Data
2016-07-29
Autores
Luperini, Bruno Cesar Ottoboni [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A obesidade é uma desordem multifatorial que envolve agentes hereditários, ambientais e estilo de vida, e suas consequências não são apenas sociais ou psicológicas, mas estão também relacionadas à presença de comorbidades como hipertensão arterial, diabetes tipo 2, doenças cardiovasculares e vários tipos de câncer. Considerando que as alterações genéticas relacionadas à obesidade não são totalmente conhecidas, assim como não se sabe a possível ação da suplementação nutricional sobre tais alterações, o presente estudo teve como objetivo avaliar a relação entre a ingestão de micronutrientes, alterações genéticas e perfil inflamatório em um grupo de 30 mulheres com obesidade mórbida, com idade entre 20 e 45 anos e submetidas à cirurgia bariátrica. A suplementação nutricional consistiu da ingestão (pó diluído em água) de vitaminas e micronutrientes correspondentes a duas DRIs (Ingestão Dietética de Referência) por dia, durante 10 semanas antes e 24 após a cirurgia bariátrica. O total de 30 mulheres eutróficas saudáveis, não fumantes e pareadas por idade às obesas, constituiu o grupo de referência. Todos os parâmetros avaliados nas mulheres obesas foram mensurados em três momentos: antes da suplementação nutricional (M1); 8 semanas após o início da suplementação e uma semana antes da cirurgia bariátrica (M2); e seis meses após o procedimento cirúrgico (M3). Os testes do cometa e do micronúcleo foram utilizados para medir, respectivamente, os níveis de danos primários no DNA e as frequências de alterações citogenéticas em células do sangue periférico. As mulheres obesas, nos três momentos mensurados, apresentaram maiores níveis (p < 0,05) de danos no DNA que as eutróficas (grupo controle). No entanto, seis meses após a cirurgia bariátrica, foi significativa a redução dos danos, quando consideradas apenas as obesas, muito embora os níveis não voltassem a atingir valores próximos ao do grupo controle. Frequências aumentadas de células micronucleadas foram detectas nas mulheres obesas antes da cirurgia bariátrica em relação as eutróficas. Contudo, seis meses após a cirurgia a frequência diminuiu significativamente, ficando semelhante à do grupo controle. Diminuições significativas de citocinas inflamatórias foram observadas nas mulheres obesas, tanto após o início da suplementação de micronutrientes, como após a cirurgia. A avaliação do perfil de expressão gênica pela técnica de microarranjos de DNA mostrou que as mulheres obesas, antes da suplementação nutricional, apresentavam hiperexpressão de genes relacionados a vias de metabolismo energético e lipídico e perfil inflamatório. Após a suplementação, foram observadas modificações no perfil de expressão desses genes, além da modulação de genes de vias como viabilidade celular e reparo de DNA. Por outro lado, após o procedimento cirúrgico e a concomitante suplementação nutricional ocorreu modulação de genes envolvidos em vias de metabolismo energético e processos inflamatórios, possivelmente devido à significativa perda de peso e consequente diminuição do IMC. Concluindo, do ponto de vista genético, este estudo demonstrou a importância da suplementação nutricional em mulheres com obesidade mórbida, antes e após a cirurgia bariátrica, embora não tivesse sido possível discriminar a extensão dos seus efeitos frente à perda de peso ocorrida após o procedimento cirúrgico.
Obesity is a complex disease that originates from a combination of social, environmental and genetic factors. Furthermore, it is associated with comorbidities such as hypertension, type 2 diabetes, heart disease and various types of cancers. Since the relationship among genetic alterations, nutritional supplementation and obesity are not fully understood, this study aimed to evaluate the effects of micronutrient intake on genetic and inflammatory profile in a group of 30 morbidly obese women, aged between 20 and 45 years and undergoing bariatric surgery. The nutritional intervention consisted of two recommended dietary allowance (RDA) of vitamins and micronutrients per day, for 10 weeks before and 24 after the bariatric surgery. A total of 30 healthy normal-weight, non-smokers and matched for age to the obese women were recruited as a control group. All the checked endpoints in obese the women were measured at three moments: before nutritional supplementation (M1); 8 weeks after beginning of supplementation and one week before bariatric surgery (M2); and six months after surgery with simultaneous nutritional supplementation (M3). The comet and micronucleus tests were used to measure the levels of primary DNA damage and the frequency of cytogenetic changes in peripheral blood cells, respectively. Obese women at the three measured moments, presented higher levels (p <0.05) of DNA damage than the control group. However, six months after the bariatric surgery the genetic damage was significantly reduced compared to the obese women before nutritional supplementation, but the amount did not reached the control group level. Similarly, increased frequencies of micronucleated cells were detected in obese women before bariatric surgery compared to the control group. However, six months after surgery this frequency decreased significantly, being similar to that in the control group. Significant reduction of inflammatory cytokines was observed in obese women after four weeks after the beginning of nutritional, as well as after surgery. Gene expression profiling was investigated using DNA microarrays. Data showed upregulation of genes related to energy and lipid metabolism, and also to inflammatory pathways in obese women before nutritional supplementation. Changes in these gene expression and also modulation of gene associated to cell viability and DNA repair pathways were observed after the nutritional supplementation. Six month after the surgical procedure and nutritional supplementation genes involved in energy metabolism and inflammatory pathways were modulated, probably due to the significant weight loss. In conclusion, this study showed the importance of nutritional supplementation, both before and after bariatric surgery. However, it was not possible to distinguish the extension of its effects after surgery because of the weight loss.
Obesity is a complex disease that originates from a combination of social, environmental and genetic factors. Furthermore, it is associated with comorbidities such as hypertension, type 2 diabetes, heart disease and various types of cancers. Since the relationship among genetic alterations, nutritional supplementation and obesity are not fully understood, this study aimed to evaluate the effects of micronutrient intake on genetic and inflammatory profile in a group of 30 morbidly obese women, aged between 20 and 45 years and undergoing bariatric surgery. The nutritional intervention consisted of two recommended dietary allowance (RDA) of vitamins and micronutrients per day, for 10 weeks before and 24 after the bariatric surgery. A total of 30 healthy normal-weight, non-smokers and matched for age to the obese women were recruited as a control group. All the checked endpoints in obese the women were measured at three moments: before nutritional supplementation (M1); 8 weeks after beginning of supplementation and one week before bariatric surgery (M2); and six months after surgery with simultaneous nutritional supplementation (M3). The comet and micronucleus tests were used to measure the levels of primary DNA damage and the frequency of cytogenetic changes in peripheral blood cells, respectively. Obese women at the three measured moments, presented higher levels (p <0.05) of DNA damage than the control group. However, six months after the bariatric surgery the genetic damage was significantly reduced compared to the obese women before nutritional supplementation, but the amount did not reached the control group level. Similarly, increased frequencies of micronucleated cells were detected in obese women before bariatric surgery compared to the control group. However, six months after surgery this frequency decreased significantly, being similar to that in the control group. Significant reduction of inflammatory cytokines was observed in obese women after four weeks after the beginning of nutritional, as well as after surgery. Gene expression profiling was investigated using DNA microarrays. Data showed upregulation of genes related to energy and lipid metabolism, and also to inflammatory pathways in obese women before nutritional supplementation. Changes in these gene expression and also modulation of gene associated to cell viability and DNA repair pathways were observed after the nutritional supplementation. Six month after the surgical procedure and nutritional supplementation genes involved in energy metabolism and inflammatory pathways were modulated, probably due to the significant weight loss. In conclusion, this study showed the importance of nutritional supplementation, both before and after bariatric surgery. However, it was not possible to distinguish the extension of its effects after surgery because of the weight loss.
Descrição
Palavras-chave
Obesidade mórbida, Suplementação nutricional, Lesões gênicas, Perfil inflamatório, Expressão gênica, Morbid obesity, Nutritional supplementation, DNA damage, Inflammatory profile