Determining mechanisms of miRNA-mediated macrophage adipocyte crosstalk

Author(s)

Andréa Livia Rocha

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2020-11-25

Examining board members

Marcelo Alves Mori; Daniel Martins de Souza; Luiz Osório Leiria; William Tadeu Lara Festuccia; Kelly Grace Magalhães

• Advisor: Marcelo Alves Mori; Renato Vicentini

Abstract

Obesity is an epidemic disease with severe health complications. The recruitment of beige adipocytes into white adipose tissue - a phenomenon called browning - results in induced thermogenesis and increased energy expenditure, representing a promising intervention to treat the disease and its complications. Published data suggest that some immune cells residing in adipose tissue, when stimulated by cold, for example, can promote the recruitment of beige adipocytes. The miRNAs were also implicated in the regulation of adipogenesis and maintenance of brown/beige adipocytes. AdicerKO mice, DICER knockout specific in adipocytes - an enzyme responsible for miRNA processing - have a partial lipodystrophy phenotype associated with the reduction of brown/beige adipocyte markers and insulin resistance. Consistent with these observations, the objective of this study is to track possible molecules capable of establishing such communications. Our data indicate that the absence of DICER in adipocytes alters the macrophages resident population in subcutaneous adipose tissue of young mice, resulting in a proinflammatory environment before any other pathophysiological or morphological alterations in adipose tissue. Consistently, we showed that the lack of DICER in adipocytes alters energy metabolism and the biosynthesis of several lipids that may contribute to reprogramming macrophages to enhance the production of IL-1?, a proinflammatory cytokine. We observed in a co-culture system that macrophages limit the Ucp1 induction in beiges adipocytes, possibly via DICER, establishing the communication between macrophages and adipocytes. This phenomenon may indicate a new mechanism of DICER in adipocytes mediating inflammation in individuals with metabolic diseases, such as obesity and diabetes (AU)