Evaluation of let7 and lin28 and the related effects on glucose homeostasis in offspring from obese dams

Abstract

In recent decades, obesity has acquired epidemic characteristics and among women this disease becomes more worrisome. Arising from changes in embryonic development and lactation period, as lack or excess of nutrients can lead to a phenomenon known as metabolic programming. Epigenetics has been demonstrated as an important factor that links the intrauterine environment and the offspring metabolism. Among the existing epigenetic modifications, microRNAs play a key role, participating in post-transcriptional regulation of several proteins. Let-7 microRNA was one of the first to be discovered and recent studies have pointed out the possible participation of Let-7 in energy homeostasis. Lin28 is a protein that modulates the expression of this miRNA. The overexpression of Lin28 and decrease of Let-7 in animal model is able to increase the uptake of glucose by improving insulin signaling, involving PI3K and m-TOR, besides of decreasing fat mass and improving sensitivity to insulin in peripheral tissues. Therefore, our goal is to investigate the hypothesis that maternal obesity modulates the Let-7 expression and Lin-28 in the offspring and that this modulation may be responsible for changes in glucose homeostasis and oxidative metabolism in offspring of obese dams. (AU)