Determining Mechanisms of miRNA-mediated Macrophage-Adipocyte Crosstalk

• Grant number: 19/10592-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: October 08, 2019
• End date: October 07, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Andréa Livia Silva Rocha
• Supervisor: Alan Saghatelian
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Salk Institute For Biological Studies, United States
• Associated to the scholarship: 16/12294-7 - Dicer signalling in adipocytes controlling immune function and activation of beige cells in adipose tissue, BP.DR

Abstract

Obesity is an epidemic disease with serious health complications. The recruitment of beige adipocytes in white adipose tissue - a phenomenon called browning - results in induced thermogenesis and increased energy expenditure and represents a promising intervention to target obesity and related diseases. Upon cold stimulation, macrophages in the adipose tissue polarize towards an M2 phenotype and help promoting the recruitment of beige adipocytes. MiRNAs have also been implicated in the regulation of adipogenesis and in the maintenance of functional identity of brown/beige adipocytes. Consistent with these observations, AdicerKO mice with adipocyte-specific knockout of Dicer - an enzyme responsible for miRNA processing - show partial lipodystrophy associated with reduced brown/beige adipocyte markers and insulin resistance. Our current data show that the absence of Dicer in adipocytes changes the population of resident immune cells in adipose tissue of young mice, resulting in a proinflammatory milieu prior to any other pathophysiological or morphological change in adipose tissue. Consistently, we demonstrate that Dicer KO adipocytes release factors that contribute to reprogram macrophages and increase the production of pro-inflammatory cytokine IL-1b. The purpose of this study is to screen the possible molecules capable of establishing the communication between adipocytes and macrophages. Exploring how Dicer in adipocytes controls the remodeling of resident immune cells in adipose tissue and impacts on inflammation and the development of beige adipocytes can reveal important mechanisms to prevent obesity and its deleterious consequences.