Low salt intake during gestation: evaluation of the epigenetic mechanisms responsible for the low birth weight and insulin resistance in adult offspring

Abstract

Barker and colleagues found an association between unfavorable environment, particularly inadequate maternal nutrition during the perinatal period with a predisposition to cardiovascular disease, metabolic and endocrine diseases in adulthood. Several epidemiological studies have found that the nutritional prenatal and early postnatal may be associated with glucose intolerance, insulin resistance, cardiovascular disease, obesity and other diseases developed in adulthood. Previous studies from our laboratory suggest that a low sodium diet during pregnancy and lactation affects fetal development and may be responsible for metabolic disorders in adulthood. One of these studies showed for the first time an association between maternal sodium restriction during the perinatal period and low birth weight and insulin resistance in adulthood. The epigenetic modifications have been proposed as likely mechanisms of fetal programming changes, but studies in this area are limited. It is understood by epigenetic modification, transmission of phenotypes from one generation to the next in the absence of structural alterations of the DNA. DNA methylation is one such mechanism. The composition of the diet consumed by adult rats during pregnancy may influence the degree of DNA methylation in the fetus and lead to disturbances in organogenesis. Thus, the purpose of this study is to assess whether epigenetic modifications may be the factors responsible for low birth weight and insulin resistance in adult life of the offspring, caused by sodium restriction in the maternal diet during pregnancy; determine which gestational period, the maternal low-sodium diet is responsible for the low birth weight of offspring; assess the gene expression of the genes of signaling pathways of insulin-like growth factor 1 and insulin target tissues of leptin on glucose metabolism and to evaluate the degree of DNA methylation the aforementioned genes presenting a change in gene expression. For both Wistar rats with twelve weeks of age, fed with a hypo or normosodic diet will be mated and the offspring will be assessed from birth to adulthood. (AU)