The role of microRNA-22 in mice metabolic complications due to maternal obesity

• Grant number: 18/13793-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 01, 2018
• End date: October 31, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Alice Cristina Rodrigues
• Grantee: Erica de Sousa
• Supervisor: Da Zhi Wang
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Harvard University, Boston, United States
• Associated to the scholarship: 16/08202-0 - Evaluation of adipose tissue microRNA expression regulating neuro-adipose crosstalk in hyperlipidic diet induced obese mice offspring, BP.DR

Abstract

Obesity has been raising worldwide in an alarming way. It is well known that risk factors for obesity are a combination from genetics and environmental factors that lead to a chronically unbalanced energy intake relative to its expenditure. Obesity in women of reproduction age is particularly concerning as there is overwhelming evidence that being born to an obese mother not only has immediate detrimental effects on the mother and neonate, but also increases the risk for the child of developing metabolic disorders in later life. This could partially be explained by transmission of obesity susceptibility genes from mother to child. Nevertheless, compelling evidence from studies in animals suggest that epigenetics mechanisms programmed in utero development in an obesogenic environment play an important role. Concerning the epigenetics mechanisms in obesity, microRNAs were found to be deregulated in adipose tissue of diet-induced obesity, after chronic cold exposure, and of offspring of obese dams, suggesting they may play a role in the development of obesity. Communication between adipose tissue and nervous system regulates energy expenditure, which is modified by obesity. In this context, brown adipose tissue has been implicated as an important site of facultative energy expenditure, and its deficiency results in obesity in the absence of hyperphagia. White adipose tissue, distinguished from brown adipocytes by virtue of their unilocular fat droplet, peripherally placed nucleus and few mitochondria, contain cells that can express high levels of UCP1 and take on a multilocular appearance upon prolonged stimulation by cold, which increases sympathetic drive. Biomedical interest in brown and beige adipocytes has centered on the therapeutically potential of both cells to counteract obesity. A previous study showed that loss of miR-22-3p in male mice increased energy expenditure and promoted a smaller fat expansion after high fat diet. In order to prove the role of miR-22 in alteration of adipose tissue remodeling in offspring of obese dams, we propose to study this model of intergenerational obesity in a miR-22 knockout background.The present research proposal aims to investigate the role of miR-22 in intergerational obesity and its metabolic alterations. Our hypothesis is that obese dam´s female pups lacking miR-22 expression have increased adiposity, and are more responsive to diet-induced obesity and less responsive to therapeutically approaches like exercise than in lean dam offspring.