Evaluation of the expression of miR-370 and miR-122 and its participation in the regulation of the process of regeneration in offispring of obese mice submitted to partial hepatectomy surgery

Author(s)

Marina Figueiredo Fontana

• Document type: Master's Dissertation
• Press: Limeira, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas
• Defense date: 2018-04-17

Examining board members

Adriana Souza Torsoni; Mara Sanches Guaragna; Maria Cláudia Gonçalves de Oliveira

• Advisor: Adriana Souza Torsoni

Abstract

In recent decades obesity has become a public health problem. During pregnancy, overweight and obesity may carry an increased risk for gestational complications and permanent changes in offspring resulting from a process known as metabolic scheduling. Different epigenetic mechanisms are capable of modulating the expression of several genes and the differential expression of microRNAs represents one of these mechanisms. Obese individuals are at increased risk for the development of hepatic abnormalities, such as non-alcoholic fatty liver disease (NAFLD), which can progress to extremely severe conditions requiring surgical intervention, with removal of injured tissue to preserve organ function, given the ability regeneration of this tissue. Several pathways are activated in the hepatic regeneration process, among them the Hippo / YAP pathway and the TGF? pathway. The Hippo / YAP pathway plays a very important role in the control of organ size, whereas TGF? is responsible for blocking the cell cycle. Using offspring from Swiss mice, who consumed a control diet or a high-fat diet during pregnancy and lactation, who underwent partial hepatectomy surgery in their adulthood, we could observe that up to 48 hours after partial hepatectomy surgery, apparently both offspring of control mothers, as far as the offspring of hyperlipidic mothers, has the capacity to regenerate the tissue to the point of maintaining the survival rate in 100% of the individuals. Alterations in miR-370 and miR-122 levels appear to have very little impact on the expression of TGF? and Hippo pathway key proteins, reducing immaterially the hepatocyte proliferation markers without causing major changes in lipid deposition in these cells . Possibly the observed results are a reflection that the survival mechanisms of the offspring stand out to the epigenetic modifications induced by the mother's diet (AU)

• FAPESP's process: 15/20991-7 - Evaluation of hepatic regeneration capacity and differential microRNAs expression in offspring from obese dams after a partial hepatectomy procedure
• Grantee: Marina Figueiredo Fontana
• Support Opportunities: Scholarships in Brazil - Master