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

• Grant number: 15/26088-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2016
• End date: August 31, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Mariana Kiomy Osako
• Grantee: Flávia Sayuri Matsuo
• Host 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.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PRZYGODDA, FRANCIELE; LAUTHERBACH, NATALIA; BUZELLE, SAMYRA LOPES; GONCALVES, DAWIT ALBIEIRO; ASSIS, ANA PAULA; PAULA-GOMES, SILVIA; RISSATO GAROFALO, MARIA ANTONIETA; HECK, LILIAN CARMO; MATSUO, FLAVIA SAYURI; MOTA, RYERSON FONSECA; et al. Sympathetic innervation suppresses the autophagic-lysosomal system in brown adipose tissue under basal and cold-stimulated conditions. Journal of Applied Physiology, v. 128, n. 4, p. 855-871, APR 2020. (12/24524-6, 18/10089-2, 16/00508-2, 15/26088-7, 14/11092-6, 13/17111-0, 12/18861-0)

MOTA, RYERSON FONSECA; DE ARAUJO, PAULO HENRIQUE CAVALCANTI; CEZINE, MARIA EDUARDA RAMOS; MATSUO, FLAVIA SAYURI; METZNER, RODRIGO JAIR MORANDI; DE BIAGI JUNIOR, CARLOS ALBERTO OLIVEIRA; PERONNI, KAMILA CHAGAS; HAYASHI, HIROKI; SHIMAMURA, MUNEHISA; NAKAGAMI, HIRONORI; et al. RANKL Impairs the TLR4 Pathway by Increasing TRAF6 and RANK Interaction in Macrophages. BIOMED RESEARCH INTERNATIONAL, v. 2022, p. 13-pg., 2022-04-12. (16/22009-8, 16/00508-2, 14/11092-6, 16/00651-0, 15/26088-7)