The involvement of the microRNA biogenesis pathway in the process of adipocyte differentiation

• Grant number: 13/26231-9
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Effective date (Start): March 17, 2014
• Effective date (End): August 16, 2014
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Beatriz Alves Guerra
• Supervisor: Tim Julius Schulz
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Research place: German Institute of Human Nutrition Potsdam-Rehbruecke, Germany
• Associated to the scholarship: 12/07259-7 - Evaluation of miRNA Processing in Adipose Tissue of Mice Subjected to Caloric Restriction, BP.MS

Abstract

Obesity is reaching epidemic proportions and leading to a worldwide increase in the prevalence of multiple comorbidities, including diabetes and cancer. Obesity is characterized by an increase in adipose tissue mass due to a positive energy balance. The adipose tissue is constituted of a functional unit called the adipocyte, which may play distinct roles depending on its developmental origin, its anatomical location or the environmental cues that control its differentiation and functional identity. In general, adipocytes are classified as white adipocytes, which store energy in form of triglycerides and secrete adipokines to control energy balance, and brown adipocytes, which are specialized in burning fat to produce heat and to maintain body temperature, and have therefore been proposed to antagonize obesity. With recent reports demonstrating the presence of brown adipocytes in adult humans and the characterization of a "browning" phenomenon in white adipose tissue of mammals, i.e. the appearance of inducible or recruitable brown adipocytes (named beige or brite) in white fat depots upon ²-adrenergic stimuli, the concept of reengineering fat to prevent obesity has been currently under extensive consideration. Understanding how adipocytes are set to develop into different functional units is a key question in this field. In this study, we will pursue the involvement of the microRNA biogenesis pathway in the process of adipocyte differentiation, since our previous results point to an important role of Dicer, a major component of this pathway, in the determination of brown adipocyte identity. As an initial approach, we will sort adipogenic progenitors from different tissues of mice in response to stimuli that induce "browning" to ask whether these cells express different levels of miRNAs and/or components of the miRNA processing pathway. We will also differentiate these cells in culture to understand whether the levels of miRNAs or the potential for miRNA synthesis correlates with the differentiation capacity and/or the identity of the adipocytes. Together with our preliminary data, these studies will bring insights into a new pathway of brown adipogenesis, providing us with more candidates to pursue interventions to prevent obesity and its complications. (AU)