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Effects of LXRs receptor activation on systemic metabolic parameters and on the metabolic modulation of resident tissue macrophages of adipose tissue

Grant number: 17/00079-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2017
Effective date (End): January 31, 2022
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Pedro Manoel Mendes de Moraes Vieira
Grantee:Jéssica Aparecida da Silva Pereira
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:15/15626-8 - Macrophages and T lymphocytes immunometabolism in metabolic and inflammatory diseases, AP.JP
Associated scholarship(s):19/04780-7 - AHR and LXR Transcriptional factors as targets to treat immune-mediated degenerative diseases, BE.EP.DR

Abstract

The functions played for macrophages are influenced by endogenous and exogenous factors, which active or inhibit innumerous signaling pathway, playing an important role as link between cellular metabolism and immune functions. The state of macrophage activation is an important factor for development of metabolic disorders, and, besides, the macrophage presence in different sites may implicate in adaptation specific-tissue of their functions. The resident adipose tissue macrophage (ATMs) need adapt their functions in response to systemic metabolic changes, like in obesity. Changes in ATMs are correlate with insulin resistance development in obesity and atherosclerosis. The LXR (Liver X receptors) are transcription factors activated by sterols involved in the metabolism of cholesterol, highly expressed in immune cells. Its activation plays an important anti-inflammatory role through the positive modulation of the expression of anti-inflammatory cytokines or by the inhibition of pro-inflammatory transcription factors such as NFºB. Several papers have attributed to LXRs important role in macrophage polarization (M1/M2). However, the way in which LXRs modulate macrophage function in vivo and how the activation of these transcription factors affects the metabolism of these cells and the development of insulin resistance is poorly understood. Based on this, our hypothesis is that the activation of LXRs is able to induce the polarization of ATMs to an M2 profile, providing a lower inflammation in the adipose tissue, leading to the improvement of the insulin sensitivity. Thus, with this project we intend to analyze how LXRs modulate the function and metabolism of ATMs and the impact that their deletion can promote on the polarization of these cells.

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Scientific publications (4)
(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)
MONTEIRO, LAUAR; DA SILVA PEREIRA, JESSICA APARECIDA; PALHINHA, LOHANNA; MORAES-VIEIRA, PEDRO MANOEL M.. Leptin in the regulation of the immunometabolism of adipose tissue-macrophages. Journal of Leukocyte Biology, v. 106, n. 3, SI, p. 703-716, . (16/23328-0, 15/15626-8, 17/00079-7)
CORREA-DA-SILVA, FELIPE; PEREIRA, JESSICA A. S.; DE AGUIAR, CRISTHIANE F.; DE MORAES-VIEIRA, PEDRO M. M.. Mitoimmunitywhen mitochondria dictates macrophage function. Cell Biology International, v. 42, n. 6, SI, p. 651-655, . (17/12848-5, 15/15626-8, 17/06225-5, 17/00079-7)
SOUZA-ALMEIDA, GLAUCIA; PALHINHA, LOHANNA; LIECHOCKI, SALLY; DA SILVA PEREIRA, JESSICA APARECIDA; REIS, PATRICIA ALVES; BRAGA DIB, PAULA RIBEIRO; HOTTZ, EUGENIO D.; GAMEIRO, JACY; VALLOCHI, ADRIANA LIMA; DE ALMEIDA, CECILIA JACQUES; et al. Peripheral leptin signaling persists in innate immune cells during diet-induced obesity. Journal of Leukocyte Biology, v. 109, n. 6, p. 1131-1138, . (15/15626-8, 19/04780-7, 17/00079-7)
DA SILVA, FELIPE CORREA; AGUIAR, CRISTHIANE; PEREIRA, JESSICA A. S.; MONTEIRO, LAUAR DE BRITO; DAVANZO, GUSTAVO GASTAO; CODO, ANA CAMPOS; DE FREITAS, LEONARDO PIMENTEL; BERTI, ALINE SIQUEIRA; FERRUCCI, DANILO LOPES; CASTELUCCI, BIANCA GAZIERI; et al. Ghrelin effects on mitochondrial fitness modulates macrophage function. Free Radical Biology and Medicine, v. 145, p. 61-66, . (17/23679-0, 16/18031-8, 17/12848-5, 18/22505-0, 15/15626-8, 17/00079-7, 17/06225-5)

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