Exercise training in male mice (Fº) and epigenetic repercussions on the molecular and functional mechanisms of insulin action and secretion in the offspring

Author(s)

José Maria Costa Junior

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2016-08-26

Examining board members

Everardo Magalhães Carneiro; Licio Augusto Velloso; Ronaldo de Carvalho Araujo; João Bosco Pesquero; César Renato Sartori

• Advisor: Camila Aparecida Machado De Oliveira; Everardo Magalhães Carneiro

Abstract

Environmental factors can affect various genetic factors through epigenetic modifications, these changes also occur in germ cells and transmitted to offspring. The vast majority of previous studies have been focus on the effects of food intake on the next generation. In the first article, we demonstrated that parental training might positively contribute to glucose homeostasis with the standard diet fed offspring, leading to increased glucose tolerance due to improved insulin sensitivity. These effects were associated with increased expression of the gene PI3Kca and IGF-2, both related to increasing insulin signaling pathway in skeletal muscle, whereas imprinted H-19 gene expression was repressed by parental training. The change in gene expression was associated with epigenome modifications with changes in DNA methylation related to their genes. Interestingly, we found that DNA methylation in the sperm tissue progenitors showed high similarity to epigenetic alterations observed in skeletal muscle of offspring. In the second article, we evaluated the effect of parental training in offspring made up of male mice fed high-fat diet. In this case, parental training induced a potentiation of the deleterious effects of high-fat diet on insulin sensitivity, leading to a dramatic glucose intolerance associated with a inability to compensates the insulin resistance with the increment of insulin secretion. The damage observed in the function of pancreatic islets were associated with reduced expression of the master transcription factor HNF4 of pancreatic beta cells, probably due to increased DNA methylation in the promoter region of mentioned gene. Our findings indicate that parental training alters susceptibility to the development of diseases related with glycemic control disorders in a positive or negative way, depending on the environment where the offspring is exposed. And it allows us to suggest that the orientation of possible modifications of the individual's lifestyle should consider the early life history of the parents (AU)

• FAPESP's process: 11/23605-0 - Exercise training in male mice (F0) and epigenetic repercussions on the molecular and functional mechanisms of insulin secretion of the offsprings (F1) fed a high fat diet
• Grantee: José Maria Costa Júnior
• Support Opportunities: Scholarships in Brazil - Doctorate