Obesity is characterized by excessive growth of adipose tissue depots either due to an increase in adipocyte number (hyperplasia) or cell size (hypertrophy) compromising the health of individuals. Studies have shown that sub-optimal maternal nutrition during pregnancy negatively influences fetal growth and development, demonstrating maternal influence, particularly during fetal life, on fetal development, and thus modifying the risk of developing some metabolic diseases in adulthood, such as obesity and type 2 diabetes. Metabolic programming is a consequence of alterations in epigenetic mechanisms that include DNA methylation, histone variants/modifications, chromatin-modifying proteins and non-coding RNAs. In this context, the role of miRNAs as epigenetic mediators of suboptimal fetal nutrition on long-term health has been studied. microRNAs are regulated by multiple factors and one miRNA can modulate the expression of a network of target mRNAs. Studies have shown that programming of proteins in the insulin-signalling pathway occurs by post-transcriptional mechanisms that involve altered miRNA concentrations, for example miR126 is programmed by maternal obesity and leads to down regulation of its direct target insulin receptor substrate 1 (IRS-1). Knowing that metabolic programming alters miRNAs, the aim of this project is to establish the full spectrum of miRNAs in adipose tissue that are programmed by maternal obesity by a small RNA sequencing in adipocytes isolated from mouse offspring during their adulthood. Mice female C57BL/6J with four weeks-old will be fed ad libitum either a standard control diet or a highly palatable energy-rich obesogenic diet, for 6 weeks before mating for first pregnancy. The tissues will be collected for maturate adipocyte and pre-adipocyte isolation, analysis and validation the mature adipocyte small RNA sequencing data, culture of isolated pre-adipocytes, isolation of exosomes from cultured pre-adipocytes for determination of their miR-126 content and statistical analysis.
News published in Agência FAPESP Newsletter about the scholarship: