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

• Grant number: 15/50650-7
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2017
• End date: October 31, 2019
• Field of knowledge: Biological Sciences - Immunology - Immunochemistry
• Agreement: AUF
• Principal Investigator: Alessandra Pontillo
• Grantee: Alessandra Pontillo
• Principal researcher abroad: Marcelo Hill
• Institution abroad: Universidad de la República (UDELAR), Uruguay
• Host 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)

Scientific publications

(8)

(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)

CORDEIRO LEAL, VINICIUS NUNES; REIS, EDIONE CRISTINA; FERNANDES, FERNANDA PEREIRA; DA SILVA SOARES, JAINE LIMA; COSTA OLIVEIRA, IOHANA GABRIELY; DE LIMA, DHEMERSON SOUZA; LARA, AMANDA NAZARETH; LOPES, MARTA HELOISA; PONTILLO, ALESSANDRA. Common pathogen-associated molecular patterns induce the hyper-activation of NLRP3 inflammasome in circulating B lymphocytes of HIV-infected individuals. AIDS, v. 35, n. 6, p. 899-910, MAY 1 2021. (15/23395-6, 18/04361-1, 15/50650-7, 15/17373-0, 17/10824-1)

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; et al. Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes. SCIENCE ADVANCES, v. 6, n. 10, MAR 2020. (14/09964-5, 15/23395-6, 14/20451-0, 17/03939-7, 11/19048-8, 17/05782-8, 13/16417-8, 16/07030-0, 12/16525-2, 12/04755-3, 15/50650-7, 18/20468-0, 13/00981-1, 11/17880-8, 15/06106-0)

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.; et al. 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. (15/20432-8, 15/23395-6, 15/50650-7)

FERNANDES, FERNANDA PEREIRA; CAMBUI, RAYLANE ADRIELLE GONCALVES; SOARES, JAINE LIMA DA SILVA; REIS, EDIONE CRISTINA DOS; LEAL, VINICIUS NUNES CORDEIRO; PONTILLO, ALESSANDRA. Cervical carcinoma induces NLRP3 inflammasome activation and IL-1ss release in human peripheral blood monocytes affecting patients' overall survival. Clinical & Translational Oncology, v. 25, n. 11, p. 10-pg., 2023-06-16. (17/10824-1, 19/06363-4, 15/50650-7, 18/04361-1, 15/17373-0)

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. (15/50650-7, 15/23395-6)

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. (15/23395-6, 15/50650-7)

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. (15/23395-6, 13/06142-1, 15/50650-7)

STEINER, ANNEMARIE; REYGAERTS, THOMAS; PONTILLO, ALESSANDRA; CECCHERINI, ISABELLA; MOECKING, JONAS; MOGHADDAS, FIONA; DAVIDSON, SOPHIA; CAROLI, FRANCESCO; GROSSI, ALICE; MORATO CASTRO, FABIO FERNANDES; et al. ecessive NLRC4-Autoinflammatory Disease Reveals an Ulcerative Colitis Locu. JOURNAL OF CLINICAL IMMUNOLOGY, v. 42, n. 2, NOV 2021. (15/50650-7, 15/23395-6)