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1.
Nutrients ; 7(5): 3370-86, 2015 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-26007332

RESUMEN

During pregnancy, selenium (Se) and folate requirements increase, with deficiencies linked to neural tube defects (folate) and DNA oxidation (Se). This study investigated the effect of a high-fat diet either supplemented with (diet H), or marginally deficient in (diet L), Se and folate. Pregnant female mice and their male offspring were assigned to one of four treatments: diet H during gestation, lactation and post-weaning; diet L during gestation, lactation and post-weaning; diet H during gestation and lactation but diet L fed to offspring post-weaning; or diet L during gestation and lactation followed by diet H fed to offspring post-weaning. Microarray and pathway analyses were performed using RNA from colon and liver of 12-week-old male offspring. Gene set enrichment analysis of liver gene expression showed that diet L affected several pathways including regulation of translation (protein biosynthesis), methyl group metabolism, and fatty acid metabolism; this effect was stronger when the diet was fed to mothers, rather than to offspring. No significant differences in individual gene expression were observed in colon but there were significant differences in cell cycle control pathways. In conclusion, a maternal low Se/folate diet during gestation and lactation has more effects on gene expression in offspring than the same diet fed to offspring post-weaning; low Se and folate in utero and during lactation thus has persistent metabolic effects in the offspring.


Asunto(s)
Ácido Fólico/administración & dosificación , Lactancia , Hígado/metabolismo , Fenómenos Fisiologicos Nutricionales Maternos , Redes y Vías Metabólicas/genética , Selenio/administración & dosificación , Destete , Animales , Dieta Alta en Grasa , Grasas de la Dieta/administración & dosificación , Femenino , Ácido Fólico/metabolismo , Ácido Fólico/farmacología , Deficiencia de Ácido Fólico/complicaciones , Expresión Génica , Hígado/efectos de los fármacos , Masculino , Redes y Vías Metabólicas/efectos de los fármacos , Ratones Endogámicos C57BL , Análisis por Micromatrices , Micronutrientes/administración & dosificación , Micronutrientes/deficiencia , Micronutrientes/metabolismo , Embarazo , Complicaciones del Embarazo , Selenio/deficiencia , Selenio/metabolismo , Selenio/farmacología
2.
BMC Med Genomics ; 6: 7, 2013 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-23497688

RESUMEN

BACKGROUND: Consumption of high-fat diets has negative impacts on health and well-being, some of which may be epigenetically regulated. Selenium and folate are two compounds which influence epigenetic mechanisms. We investigated the hypothesis that post-weaning supplementation with adequate levels of selenium and folate in offspring of female mice fed a high-fat, low selenium and folate diet during gestation and lactation will lead to epigenetic changes of potential importance for long-term health. METHODS: Female offspring of mothers fed the experimental diet were either maintained on this diet (HF-low-low), or weaned onto a high-fat diet with sufficient levels of selenium and folate (HF-low-suf), for 8 weeks. Gene and protein expression, DNA methylation, and histone modifications were measured in colon and liver of female offspring. RESULTS: Adequate levels of selenium and folate post-weaning affected gene expression in colon and liver of offspring, including decreasing Slc2a4 gene expression. Protein expression was only altered in the liver. There was no effect of adequate levels of selenium and folate on global histone modifications in the liver. Global liver DNA methylation was decreased in mice switched to adequate levels of selenium and folate, but there was no effect on methylation of specific CpG sites within the Slc2a4 gene in liver. CONCLUSIONS: Post-weaning supplementation with adequate levels of selenium and folate in female offspring of mice fed high-fat diets inadequate in selenium and folate during gestation and lactation can alter global DNA methylation in liver. This may be one factor through which the negative effects of a poor diet during early life can be ameliorated. Further research is required to establish what role epigenetic changes play in mediating observed changes in gene and protein expression, and the relevance of these changes to health.


Asunto(s)
Metilación de ADN , Dieta Alta en Grasa , Ácido Fólico/farmacología , Perfilación de la Expresión Génica , Proteoma/metabolismo , Selenio/farmacología , Animales , Animales Recién Nacidos , Análisis por Conglomerados , Islas de CpG , Suplementos Dietéticos , Femenino , Transportador de Glucosa de Tipo 4/genética , Transportador de Glucosa de Tipo 4/metabolismo , Histonas/genética , Histonas/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Regiones Promotoras Genéticas , Proteómica , Selenio/análisis , Destete
3.
Biotechnol J ; 6(1): 113-7, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21053336

RESUMEN

Epigenetic changes in chromatin structure can influence gene expression without affecting the DNA sequence. The most commonly studied epigenetic modification, DNA methylation, has been implicated in normal tissue development and disease progression, and can be influenced by diet and other environmental factors. Current HPLC methods of determining DNA methylation may require relatively large amounts of DNA (50 µg); as many tissues have low DNA yields, this can be hard to achieve. We isolated DNA from mouse colon and liver in a study investigating post-natal supplementation with selenium and folic acid. After optimizing the methods to account for lower initial DNA amounts, we digested 3 µg of DNA to deoxynucleotide monophosphates, then purified and quantified it. Samples were analyzed by reversed-phase HPLC to determine global DNA methylation levels using commercial nucleotide standards. The HPLC column was cooled to 6(C (reducing run time), and detection was at 280 nm (UV). We showed that methylated cytosine can be accurately and reproducibly measured in as little as 3 µg of DNA using this HPLC analysis method (within-assay CV <2%). We also used this method to detect reduced DNA methylation in liver (P = 0.009) in response to post-natal supplementation with selenium and folate.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Metilación de ADN/genética , Epigenómica/métodos , 5-Metilcitosina/análisis , 5-Metilcitosina/química , Animales , Colon/metabolismo , Femenino , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL
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