RESUMO
PURPOSE: We have investigated the epigenetic regulation by dietary fatty acids of Vegfb levels in rats' white adipose tissue and 3T3-L1 cells. METHODS: A group of rats were assigned to three diets, each one with a different composition of saturated, monounsaturated and polyunsaturated fatty acids. Samples of white adipose tissues were taken for the methylation and expression studies. Additionally, 3T3-L1 cells were treated with palmitic, oleic, and linoleic fatty acids. After treatment, cells were harvested and genetic material was extracted for the analysis of Vegfb levels. RESULTS: We report evidence of changes in the methylation levels of the CpG island at the Vegfb promoter and in the Vegfb expression levels in vivo and in vitro by dietary fatty acid, with the main contribution of the linoleic fatty acid. Vegfb promoter methylation levels were closely related to the Vegfb gene expression. CONCLUSION: According to our results, the regulation of Vegfb gene expression by dietary fatty acids may be mediated, at least in part, by epigenetic modifications on Vegfb promoter methylation. Considering the deep association between angiogenesis and tissue growth, we suggest the nutriepigenetic regulation of Vegfb as a key target in the control of the adipose tissue expansion.
Assuntos
Adipócitos Brancos/metabolismo , Metilação de DNA , Gorduras na Dieta/administração & dosagem , Regulação da Expressão Gênica , Regiões Promotoras Genéticas , Fator B de Crescimento do Endotélio Vascular/metabolismo , Células 3T3-L1 , Animais , Óleo de Coco , Ilhas de CpG , Gorduras na Dieta/metabolismo , Epigênese Genética , Gordura Intra-Abdominal/metabolismo , Ácido Linoleico/administração & dosagem , Ácido Linoleico/metabolismo , Masculino , Camundongos , Ácido Oleico/administração & dosagem , Ácido Oleico/metabolismo , Azeite de Oliva/administração & dosagem , Azeite de Oliva/metabolismo , Ácido Palmítico/administração & dosagem , Ácido Palmítico/metabolismo , Óleos de Plantas/administração & dosagem , Óleos de Plantas/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Gordura Subcutânea Abdominal/metabolismo , Óleo de Girassol , Fator B de Crescimento do Endotélio Vascular/genéticaRESUMO
The role of selenium exposure in preventing chronic disease is controversial, especially in selenium-repleted populations. At high concentrations, selenium exposure may increase oxidative stress. Studies evaluating the interaction of genetic variation in genes involved in oxidative stress pathways and selenium are scarce. We evaluated the cross-sectional association of plasma selenium concentrations with oxidative stress levels, measured as oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8-oxo-7,8-dihydroguanine (8-oxo-dG) in urine, and the interacting role of genetic variation in oxidative stress candidate genes, in a representative sample of 1445 men and women aged 18-85 years from Spain. The geometric mean of plasma selenium levels in the study sample was 84.76 µg/L. In fully adjusted models the geometric mean ratios for oxidative stress biomarker levels comparing the highest to the lowest quintiles of plasma selenium levels were 0.61 (0.50-0.76) for GSSG/GSH, 0.89 (0.79-1.00) for MDA, and 1.06 (0.96-1.18) for 8-oxo-dG. We observed nonlinear dose-responses of selenium exposure and oxidative stress biomarkers, with plasma selenium concentrations above ~110 µg/L being positively associated with 8-oxo-dG, but inversely associated with GSSG/GSH and MDA. In addition, we identified potential risk genotypes associated with increased levels of oxidative stress markers with high selenium levels. Our findings support that high selenium levels increase oxidative stress in some biological processes. More studies are needed to disentangle the complexity of selenium biology and the relevance of potential gene-selenium interactions in relation to health outcomes in human populations.