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Characterization of novel molecular players in the control of obesity and obesity-induced inflammation

Grant number: 15/50650-7
Support type:Regular Research Grants
Duration: November 01, 2017 - October 31, 2019
Field of knowledge:Biological Sciences - Immunology - Immunochemistry
Cooperation agreement: AUF
Principal researcher:Alessandra Pontillo
Grantee:Alessandra Pontillo
Principal researcher abroad: Marcelo Hill
Institution abroad: Universidad de la República (UDELAR), Uruguay
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Obesity is characterized by local and systemic chronic "sterile" inflammation in metabolically relevant organs and tissues.Recent findings suggest the multi-protein complex known as inflammasome plays a key role in regulating tissue inflammation during obesity and metabolic syndrome, as it is responsible for the secretion of inflammatory cytokines IL-1 B and IL-18. Recently, Hill and others have shown that the intracellular cation channel TORID is a novel and emerging key regulator of immune responses, and that it specifically inhibits inflammasome activation in vitro and in vivo. Interestingly, TORID KO mice under high fat diet displayed increased weight and insulin resistance compared to WT ones. We therefore propose to characterize the role of TORID in inflammasome activation in obesity. To carry out this objective we will: 1) study the role of TORID in obesity-induced inflammation and metabolic syndrome in mice; 2) characterize the mechanisms by which TORID regulates inflammasome activation; 3) evaluate inflammasome gene SNPs contribution in the development of obesity and obesity-related metabolic disorders in humans. We expect to determine that TORID is a novel target to control obesity-induced inflammation relevant in human biology. (AU)

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Scientific publications (5)
(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)
DE LIMA, DHEMERSON SOUZA; BOMFIM, CAIO C. B.; LEAL, VINICIUS N. C.; REIS, EDIONE C.; SOARES, JAINE L. S.; FERNANDES, FERNANDA P.; AMARAL, EDUARDO P.; LOURES, V, FLAVIO; OGUSKU, MAURICIO M.; D'IMPERIO LIMA, MARIA R.; SADAHIRO, AYA; PONTILLO, ALESSANDRA. Combining Host Genetics and Functional Analysis to Depict Inflammasome Contribution in Tuberculosis Susceptibility and Outcome in Endemic Areas. FRONTIERS IN IMMUNOLOGY, v. 11, OCT 21 2020. Web of Science Citations: 0.
GONCALVES CAMBUI, RAYLANE ADRIELLE; DO ESPIRITO SANTO, GILMAR FERREIRA; FERNANDES, FERNANDA PEREIRA; CORDEIRO LEAL, VINICIUS NUNES; GALERA, BIANCA BORSATTO; PALACIO FAVARO, EMERSON GIULIANO; RIZZO, LEONARDO AMORIM; ELIAS, ROSA MARIA; PONTILLO, ALESSANDRA. Double-edged sword of inflammasome genetics in colorectal cancer prognosis. Clinical Immunology, v. 213, APR 2020. Web of Science Citations: 0.
REIS, ARAMYS S.; BARBOZA, RENATO; MURILLO, OSCAR; BARATEIRO, ANDRE; PEIXOTO, ERIKA P. M.; LIMA, FLAVIA A.; GOMES, VINICIUS M.; DOMBROWSKI, JAMILLE G.; LEAL, VINICIUS N. C.; ARAUJO, FRANCIELE; BANDEIRA, CARLA L.; ARAUJO, ROSANA B. D.; NERES, RITA; SOUZA, RODRIGO M.; COSTA, FABIO T. M.; PONTILLO, ALESSANDRA; BEVILACQUA, ESTELA; WRENGER, CARSTEN; WUNDERLICH, GERHARD; PALMISANO, GIUSEPPE; LABRIOLA, LETICIA; BORTOLUCI, KARINA R.; PENHA-GONCALVES, CARLOS; GONCALVES, LIGIA A.; EPIPHANIO, SABRINA; MARINHO, CLAUDIO R. F. Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes. SCIENCE ADVANCES, v. 6, n. 10 MAR 2020. Web of Science Citations: 0.
REIS, EDIONE C.; LEAL, VINICIUS N. C.; DA SILVA, LAIS T.; DOS REIS, MARILIA M. L.; ARGANARAZ, ENRIQUE R.; OSHIRO, TELMA M.; PONTILLO, ALESSANDRA. Antagonistic role of IL-1 beta and NLRP3/IL-18 genetics in chronic HIV-1 infection. Clinical Immunology, v. 209, DEC 2019. Web of Science Citations: 1.
SOARES, JAINE L. S.; OLIVEIRA, ENEDINA M. L.; PONTILLO, ALESSANDRA. Variants in NLRP3 and NLRC4 inflammasome associate with susceptibility and severity of multiple sclerosis. MULTIPLE SCLEROSIS AND RELATED DISORDERS, v. 29, p. 26-34, APR 2019. Web of Science Citations: 3.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.