The involvement of microRNAs in the accelerated ageing process caused by obesity and the potential intervention by caloric restriction, fatty acid supplementation and exercise

Abstract

The incidence of maternal obesity at pregnancy is growing and the metabolic deregulation during pregnancy causes important changes in the offspring metabolism. Insulin resistance, which is closely related to the development of type 2 diabetes, could be cited as a consequence of some of these alterations. Skeletal muscle has a fundamentally important role in the maintenance of normal glucose homeostasis in response to insulin or contractile activity. However, obesity could lead to an impairment of this function by the activation of an accelerated ageing process. There is a growing body of literature suggesting that epigenetic changes play an important role for the increased incidence of chronic diseases, including type 2 diabetes. MicroRNAs are involved in crucial biological processes, including metabolism regulation. Therefore, the aim of this project is to identify the microRNAs involved in the consequences of an accelerated ageing process caused by maternal obesity in skeletal muscle of the offspring. Furthermore, the effectiveness of exercise during pregnancy, caloric restriction or fatty acid supplementation as interventions to reduce these molecular changes in skeletal muscle of the offspring will be investigated. For the purposes of this project, RNA-seq, proteomics-SILAC, in silico analysis and luciferase reporter assay will be used to achieve the goal. Thus, this project will make a valuable contribution to the understanding of the impact of maternal obesity on the health of the offspring on molecular level, as well identifying potential biomarkers for metabolic diseases as diabetes and elucidating the possible benefit of exercise, caloric restriction and fatty acid supplementation as an intervention for the effects of maternal obesity on the pups. (AU)