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RANKL system in phenotypic switch of macrophages in adipose tissue inflammation

Abstract

High serum osteoprotegerin (OPG) level has been associated with type 2 diabetes mellitus (T2DM), vascular calcification and predicts cardiovascular outcomes, but the biological explanation for the rise of OPG level remains unclear. OPG is a decoy receptor of RANKL, and the binding results in inhibition of RANKL activation of the membrane bound RANK. We have reported the contribution of this RANKL system in vascular calcification, and recent evidences suggest an important role in regulating macrophages inflammatory responses. This study aims to clarify the molecular mechanism underpinning RANKL activation in macrophages, to elucidate its role in macrophage phenotypic switch between pro- (M1) and anti-inflammatory (M2) states. The role in M1/M2 macrophages will be explored in adipose tissue inflammation and insulin resistance by focusing on toll like receptor 4 (TLR-4) pathways in murine model under high fat diet. The results obtained in this study will provide a biological explanation for the increase in serum OPG level of diabetic patients, and whether it can be considered as a contributor for the adipose tissue inflammation and eventually insulin resistance. RANKL/OPG system has the potential to become a therapeutic target to regulate macrophage activation. (AU)

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; OSAKO, MARIANA KIOMY; KETTELHUT, ISIS C.; NAVEGANTES, LUIZ C. 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. Web of Science Citations: 0.

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