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The role of maternal obesity on modulation of offspring hypothalamic miRNAs and metabolic consequences associated

Grant number: 16/07361-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2016
Effective date (End): October 04, 2019
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Licio Augusto Velloso
Grantee:Juliana de Almeida Faria
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID
Associated scholarship(s):17/03525-8 - The role of maternal obesity on modulation of offspring hypothalamic miRNAs and metabolic consequences associated, BE.EP.PD

Abstract

Obesity has reached epidemic proportions around the world, especially in urban settings. However the prevalence of obesity has expanded steadily to both genders, in 2014 the number of obese women, including those in childbearing age, exceeded that of men in the same condition in all WHO regions. Maternal obesity is associated with significant changes in the metabolism of offspring, favoring the risk of developing metabolic diseases with relevant prevalence, such as diabetes mellitus. During fetal life, organs and tissues present an intense process of cell division and growth, and this phase is defined as a critical period for human development. Stimuli, deficiencies or injuries occurred during this critical period induce permanent changes in the health of the offspring, compromising cellular function and structure. In this context, the hypothalamus has a key role in the control of glucose homeostasis through the response to nutrients consumed and, therefore, is considered a key component in the regulation of obesity effects on energy metabolism. In addition, maternal obesity has often been associated with increased offspring weight gain, which is associated with hyperphagia, resulting in losses in the central regulation of food intake as a consequence of fetal programming. The epigenetic mechanism is among the most important molecular processes related to metabolic programming and development of diseases by offspring. As epigenetics components, microRNAs are involved in key biological processes, including metabolic regulation. Thus, the purpose of this project is to identify and to investigate the involvement of microRNAs in changes caused by maternal obesity on neuronal circuits related to fedding regulation in offspring and outline the central metabolic pathways affected. Once identified metabolic pathways and the microRNAs potentially involved, we will next define new points for intervention and therapy. For that, we will employ RNA-seq techniques, proteomics-SILAC, western blot, qPCR, in silico analysis and luciferase reporter assay. This project will make a valuable contribution to the understanding of the molecular mechanisms involved in the conection between maternal obesity and dysfunction of the hypothalamus in the offspring with particular attention to the role of microRNAs and the pathways under their control.