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Evaluation of immune metabolic response in peritoneal macrophages from obese mice: role of physical exercise and PPAR-gamma

Grant number: 14/01246-6
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2015
Effective date (End): December 31, 2018
Field of knowledge:Health Sciences - Physical Education
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Fábio Santos de Lira
Grantee:Loreana Sanches Silveira
Host Institution: Faculdade de Ciências e Tecnologia (FCT). Universidade Estadual Paulista (UNESP). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil
Associated scholarship(s):17/08530-0 - The influence of PPARg on incorporation of fatty acids into placental lipid pools and their transfer to the fetus, BE.EP.DR


Moderate aerobic exercise is increasingly established as an effective non-pharmacological therapy for the prevention and treatment of aseptic chronic inflammatory diseases considered as the largest cause of death worldwide. Among these diseases, can be mentioned obesity, diabetes type 2, cardiovascular diseases in general, cancer, neurodegenerative diseases, among others. The therapeutic role of exercise training is through increased anti-inflammatory response induced by moderate exercise. Although this effect is well documented in the literature, little is known about the molecular pathways that may be involved in this process as well as whether the high intensity training is able to modulate the inflammatory response in a similar way of moderate exercise. Macrophages when chronically activated favor the onset and progression of many inflammatory diseases. There are many transcription factors that regulate the response of this cell type, including peroxisome proliferator-activated receptor gamma (PPAR-gamma), which is capable of regulating the immuno metabolic response, leading to an increase in macrophages that are characterized by M2, or is phenotypically presenting an exponential increase in the capacity to secrete anti-inflammatory cytokines and prostaglandins. This change in phenotype occurs as a result of exercise training, we aim to understand whether the PPAR-gamma is important in this process, and finally to assess whether their deletion in myeloid cells may lead to decreased anti-inflammatory response caused by exercise when a low inflammatory state level is induced, in case it occurs, by the induction of obesity in mice. To test our hypothesis, two strains of animals will be used: CreLox for PPAR-gamma (Cre + / + PPAR-gamma - / -) that lead to deletion of PPAR, specifically in myeloid cells, and animal control littermates (Cre - / - PPAR-gamma + / +). For each group of animals will be formed six subgroups with 10 animals per group: 1) balanced diet and sedentary (BS); 2) balanced diet and moderate-intensity training (BTM); 3) balanced diet and high intensity training (BTA); 4) high-fat diet and sedentary (HS); 5) high-fat diet and moderate-intensity training (HTM); 6) high-fat diet and high intensity training (HTA). Will be assessed the metabolic profile and systemic inflammation, as well as primary cultures of peritoneal macrophages, cytokine production and gene expression, protein expression and activation of PPAR-gamma. Experiments with cultured peritoneal macrophages (in vitro) and animal model will provide better understanding of the role of PPAR-gammain immune metabolic regulation. (AU)

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Scientific publications (6)
(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)
SANCHES SILVEIRA, LOREANA; MELLO ANTUNES, BARBARA DE MOURA; ARAUJO MINARI, ANDRE LUIS; THOMATIELI DOS SANTOS, RONALDO VAGNER; ROSA NETO, JOSE CESAR; LIRA, FABIO SANTOS. Macrophage Polarization: Implications on Metabolic Diseases and the Role of Exercise. CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION, v. 26, n. 2, p. 115-132, . (14/08003-1, 13/25310-2, 13/09367-4, 14/01246-6)
BATATINHA, HELENA A. P.; LIMA, EDSON A.; TEIXEIRA, ALEXANDRE A. S.; SOUZA, CAMILA O.; BIONDO, LUANA A.; SILVEIRA, LOREANA S.; LIRA, FABIO S.; ROSA NETO, JOSE C.. Association Between Aerobic Exercise and Rosiglitazone Avoided the NAFLD and Liver Inflammation Exacerbated in PPAR-alpha Knockout Mice. Journal of Cellular Physiology, v. 232, n. 5, p. 1008-1019, . (13/25310-2, 13/09367-4, 14/01246-6)
SILVEIRA, LOREANA S.; PIMENTEL, GUSTAVO D.; SOUZA, CAMILA O.; BIONDO, LUANA A.; TEIXEIRA, ALEXANDRE ABILIO S.; LIMA, EDSON A.; BATATINHA, HELENA A. P.; ROSA NETO, JOSE C.; LIRA, FABIO S.. Effect of an acute moderate-exercise session on metabolic and inflammatory profile of PPAR- knockout mice. Cell Biochemistry and Function, v. 35, n. 8, p. 510-517, . (13/09367-4, 14/01246-6, 13/10861-3, 13/04765-1, 13/25310-2)
SILVEIRA, LOREANA SANCHES; PEREIRA BATATINHA, HELENA ANGELICA; CASTOLDI, ANGELA; SARAIVA CAMARA, NIELS OLSEN; FESTUCCIA, WILLIAN T.; SOUZA, CAMILA OLIVEIRA; ROSA NETO, JOSE CESAR; LIRA, FABIO SANTOS. Exercise rescues the immune response fine-tuned impaired by peroxisome proliferator-activated receptors deletion in macrophages. Journal of Cellular Physiology, v. 234, n. 4, p. 5241-5251, . (14/01246-6, 16/01409-8, 13/25310-2)
SILVEIRA, LOREANA SANCHES; BIONDO, LUANA AMORIM; DE SOUZA TEIXEIRA, ALEXANDRE ABILIO; DE LIMA JUNIOR, EDSON ALVES; CASTOLDI, ANGELA; SARAIVA CAMARA, NIELS OLSEN; FESTUCCIA, WILLIAN T.; ROSA-NETO, JOSE CESAR; LIRA, FABIO SANTOS. Macrophage immunophenotype but not anti-inflammatory profile is modulated by peroxisome proliferator-activated receptor gamma (PPAR gamma) in exercised obese mice. EXERCISE IMMUNOLOGY REVIEW, v. 26, p. 94-106, . (18/21964-1, 13/25310-2, 14/01246-6, 16/01409-8)
CABRAL-SANTOS, CAROLINA; SILVEIRA, LOREANA SANCHES; CHIMIN, PATRICIA; ROSA-NETO, JOSE CESAR; LIRA, FABIO SANTOS. Moderate aerobic exercise-induced cytokines changes are disturbed in PPAR alpha knockout mice. CYTOKINE, v. 134, p. 7-pg., . (18/17648-7, 15/26148-0, 14/01246-6)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SILVEIRA, Loreana Sanches. Evaluation of the immuno-metabolic response in peritonal macrophages of obese mice: role of physical exercise and PPAR-γ. 2018. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Ciências e Tecnologia. Presidente Prudente Presidente Prudente.

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