FLAVIA RAMOS DE SIQUEIRA
Projetos de Pesquisa
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LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
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- Igf1 DNA methylation, epigenetics, and low-salt diet in fetal programming(2019) SIQUEIRA, F. R. De; FURUKAWA, L. N. S.; HEIMANN, J. C.All cells of an organism share the same DNA sequence from the time they are stem cells up to the time they are fully differentiated, distinct greatly in relation to the profile of expressed genes. Changes in gene expression which do not involve changes in DNA sequence of the nucleotides are currently known as an epigenetic phenomenon. Epigenetic changes play a fundamental role in the human gene expression and in the mechanism of association between events that occur early in life and alterations in adult life. Thus, in response to an adverse environment in which pregnant women are exposed during the perinatal or neonatal period, epigenetic modifications may lead to alterations in growth and metabolism in later life. Modification of histones (proteins found in eukaryotic cell nucleus) and DNA methylation (a process by which methyl groups are added to DNA) are the major epigenetic mechanisms involved in the regulation of gene expression. Maternal insults, mainly inadequate nutrition that may occur during sensitive or critical periods of fetal development (periods of rapid cell division), can program changes in the structure and functionality of cells, tissues, and/or organ systems. These changes may result in premature consequences in the offspring such as low birth weight and/or chronic diseases (hypertension, insulin resistance, obesity, etc.) in adulthood. A low-salt diet during pregnancy has been associated with low birth weight and chronic diseases in adult offspring, at least in the experimental setting. The expression of genes as insulin-like growth factors is regulated in a tissue-specific manner and can be altered by nutritional and endocrine conditions in utero. It is known that the major mediator of fetal growth is insulin-like growth factor type 1 (IGF-1) and insulin. The low birth weight may be due to low serum IGF-1 and/or by Igf1 epigenetic changes in fetus in response to low-salt intake during pregnancy. This observation might underlie the altered offspring phenotypes in this model since growth and insulin sensitivity are modulated by hepatic IGF-1. A low birth weight is related to low Igf1 gene expression and high Igf1 DNA methylation levels induced by low-salt intake during pregnancy. The variation in the IGF-1 serum levels may be due to changes in Igf1 gene promoter methylation. This concept is supported by increased methylation that is often associated with reduced gene expression. The methylation of genes changed as the offspring aged, indicating that epigenetic changes can occur and can be reversed during postnatal life. Further studies are needed to confirm or not if the observed results are reproducible in humans in order to recommend low dietary salt consumption during pregnancy. © Springer Nature Switzerland AG 2019. All rights reserved.
bookPart 0 Citação(ões) na Scopus Impact of low-salt diet(2019) SIQUEIRA, F. R. De; OLIVEIRA, K. C. De; HEIMANN, J. C.; FURUKAWA, L. N. S.Studies in experimental animals and in groups of humans and epidemiological studies have shown that the sodium chloride or salt (sodium, Na, NaCl) plays an important role mainly in the regulation of blood pressure and represents an important environmental factor involved in the genesis of cardiovascular diseases. Therefore, salt intake in the population has been a constant concern. Variable blood pressure responses to different content in sodium intake are found in experimental hypertension models and in humans, and the reasons for such heterogeneity are not fully elucidated. The reduction of dietary sodium intake is recommended by public health as one of the non-medicated treatments for hypertension and consequently reducing the risk of cardiovascular diseases. However, some studies have demonstrated side effects of salt dietary restriction, reporting changes in glucose metabolism (hyperinsulinemia and insulin resistance), and these alterations are gender and time specific in experimental and population studies. © Springer Nature Switzerland AG 2019.