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Sepsis and Obesity: study of the relationship between obesity and immune regulation in an experimental model of sepsis

Grant number: 11/15682-4
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2012
Effective date (End): August 31, 2015
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Niels Olsen Saraiva Câmara
Grantee:Angela Castoldi
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:07/07139-3 - The role of heme oxygenase 1 in different renal inflammatory process in experimental animal models, AP.TEM
Associated scholarship(s):14/02218-6 - A study of the signaling pathways induced by RBP4 in macrophages and dendritic cells in obesity-induced insulin resistance, BE.EP.DR


Obesity and metabolic syndrome are public health problems and influence the outcome of various immune diseases, besides acting as a risk factor for the severity of sepsis. The activation of innate immunity may lead to inflammation of low intensity in obesity by activation of endothelial cells, adipocytes and macrophages and synthesis of TNF-alfa, insulin resistance, and is also linked to diabetes. In addition, there are data that clearly show that obesity may be related to changes in intestinal microbiota and seems to be a risk factor "dose dependent" mortality and morbidity in sepsis. Among the genes associated with obesity, leptin has a central role. Leptin, a 16 Kd protein, is well known for its control functions of appetite and, more recently, their involvement in intestinal inflammation and sepsis. However, little is known about the exact mechanism involved in leptin signaling in cell activation and tissue dysfunction associated with sepsis. But there are indications that high leptin levels are induced by increased production of IL-1 beta and TNF- alfa during sepsis. Thus, the objective of this project is to study the relationship between obesity, leptin and intestinal microbiota in the regulation of immune response in an experimental model of sepsis in obese animals. We aim thus to contribute to understanding the relationship between obesity, gut microbiota and the regulation of immune response during an inflammatory stimulus such as severe sepsis.

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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)
LEE, JENNIFER; MORAES-VIEIRA, PEDRO M.; CASTOLDI, ANGELA; ARYAL, PRATIK; YEE, ERIC U.; VICKERS, CHRISTOPHER; PARNAS, OREN; DONALDSON, CYNTHIA J.; SAGHATELIAN, ALAN; KAHN, BARBARA B.. Branched Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) Protect against Colitis by Regulating Gut Innate and Adaptive Immune Responses. Journal of Biological Chemistry, v. 291, n. 42, p. 22207-22217, . (11/15682-4, 14/02218-6)
CASTOLDI, ANGELA; ANDRADE-OLIVEIRA, VINICIUS; AGUIAR, CRISTHIANE FAVERO; AMANO, MARIANE TAMI; LEE, JENNIFER; MIYAGI, MARCELLI TERUMI; LATANCIA, MARCELA TEATIN; BRAGA, TARCIO TEODORO; DA SILVA, MARINA BURGOS; IGNACIO, ALINE; et al. Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88. CELL REPORTS, v. 19, n. 11, p. 2272-2288, . (15/18121-4, 11/15682-4, 12/02270-2)
CASTOLDI, ANGELA; DE AGUIAR, CRISTHIANE FAVERO; MORAES-VIEIRA, PEDRO MANOEL; SARAIVA CAMARA, NIELS OLSEN. They Must Hold Tight: Junction Proteins, Microbiota And Immunity In Intestinal Mucosa. CURRENT PROTEIN & PEPTIDE SCIENCE, v. 16, n. 7, p. 655-671, . (14/10828-9, 12/02270-2, 12/16794-3, 14/02218-6, 11/15682-4)
CASTOLDI, ANGELA; DE SOUZA, CRISTIANE NAFFAH; SARAIVA CAMARA, NIELS OLSEN; MORAES-VIEIRA, PEDRO M.. The Macrophage Switch in Obesity Development. FRONTIERS IN IMMUNOLOGY, v. 6, . (15/18121-4, 11/15682-4, 12/02270-2, 14/10910-7)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
CASTOLDI, Angela. MyD88: a modulator of inflammatory and metabolic profile in experimental obesity.. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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