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Study of RANKL/RANK/OPG signaling pathway in beige adipose tissue differentiation

Grant number: 15/26088-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2016
Effective date (End): August 31, 2019
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Mariana Kiomy Osako
Grantee:Flávia Sayuri Matsuo
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:14/11092-6 - RANKL system in phenotypic switch of macrophages in adipose tissue inflammation, AP.JP

Abstract

Adipose tissue is a complex organ which has many functions in the body metabolism. The white adipose tissue can express high levels of UCP1 through beta-adrenergic stimulation and acquire a multilocular appearance, called beige adipocyte. Due to this plasticity of white adipocyte in becoming beige adipocyte ("browning"), the understanding of molecular mechanisms involved in development and maintenance of this cell type is on the spot of investigations for treatment of obesity and metabolic diseases. Recent studies have shown that cold exposure induces IL-4 activation, and anti-inflammatory profile in macrophages (M2). This activation leads to expression of tyrosine hydroxylase responsible for the catecholamines synthesis and differentiation of beige adipose tissue. It is also known that PPAR³ acts as an important regulator of alternative response maintenance in macrophages and a preliminary study of our group showed that RANKL induces PPAR³ expression. Therefore, the purpose of this project is to clarify the molecular mechanism of RANKL/PPAR³ axis contribution on M2 profile for the beige adipose tissue differentiation, and also the effect of RANKL direct contribution on the browning of white adipose tissue.

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