Role of Dicer in beige adipocyte differentiation and the influence of macrophages in this process

• Grant number: 19/07575-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): May 01, 2019
• Effective date (End): April 30, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Rhaissa Godoi
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/01184-9 - CAMeLEOm: cross-species analysis of metabolic, lifespan effects and omics of dietary restriction mimetics, AP.TEM

Abstract

Obesity affects a large part of the world population, being associated with several health complications, such as cardiovascular diseases and diabetes. Adipose tissue can either store energy, in white adipocytes, or dissipate it as heat in brown or beige adipocytes. This thermogenic process can be stimulated by cold through the browning mechanism, which is mediated mainly by uncoupling protein 1 (UCP1). A set of immune cells also resides in adipose tissue and participates in the control of adipocyte functions, through molecules such as cytokines and miRNAs (small non-coding RNA molecules, processed by the enzyme DICER, with important function in post-transcriptional regulation). The expression of miRNAs in adipose tissue is lower in obesity, and this scenario is associated with decreased expression of DICER and macrophage-mediated inflammation in the tissue. In previous data from the laboratory, it was demonstrated that the knockout of DICER in adipocytes makes subcutaneous adipose tissue more inflamed and less capable of activating a thermogenic program and cold exposure attenuates such differences. These data are corroborated by co-culture experiments with adipocytes and macrophages, in which there was inhibition of adipocyte UCP1 expression by macrophages after a thermogenic stimuli, a phenomenon that does not occur in Dicer KO adipocytes, suggesting dependence on the expression of DICER in adipocytes. Thus, it was possible to hypothesize that macrophages communicate with adipocytes during the browning process and may inhibit this process by miRNAs expressed in adipocytes. Therefore, the project aims to investigate how DICER participates in the browning mechanism and mediates the influence of macrophages in the process, in order to elucidate new mechanisms of prevention and treatment of obesity.