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T lymphocytes responses and cardiorespiratory fitness in adults: Role of adipose tissue and mTORC1 and mTORC2 pathway

Grant number: 18/23402-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): December 01, 2019
Effective date (End): November 30, 2021
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal researcher:Fábio Santos de Lira
Grantee:Camila de Souza Padilha
Home Institution: Faculdade de Ciências e Tecnologia (FCT). Universidade Estadual Paulista (UNESP). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil


Sedentary behavior, physical inactivity and unhealthy nutrition are key factors which contribute to an increased level of body adiposity, especially visceral adipose tissue. Cardiorespiratory fitness level is considered a potential modifier of the inverse association between visceral obesity and mortality. Combined to these factors, low-grade inflammation promotes insulin and adiponectin resistance and dysregulation of the adaptive immune system, as well as T lymphocytes. The energetic demand of T lymphocytes is regulated by nutrient sensors, such as mTORC, which positively contributes to cellular growth and proliferation, and also regulates T regulatory lymphocytes function. Therefore, the purpose of this study is to investigate the impacts of mTORC1 and mTORC2 pathways on Treg and Th17 lymphocytes regulation, the inflammatory responses according to low-cardiorespiratory fitness level and high-visceral adipose tissue, and high-cardiorespiratory fitness level and low-visceral adipose tissue in men and women. An initial screening will be performed to measure and classify individual body composition and nutritional habits. Participants, aged between 18 and 35 years old, will be recruited. A maximal incremental test will be performed in order to determine aerobic and anaerobic threshold, aerobic capacity, and aerobic power. Blood samples will be collected for STAT3, STAT5, TNF-±, IL-1ra, IL-6, IL-12, IL-4, IL-10, MCP-1, insulin, and cortisol measurements. In culture cells, T lymphocytes will be treated either with IL-2 to differentiate into Treg or IL-6 to differentiate into Th17. After differentiation, Treg and Th17 will be treated with rapamycin or leucine (mTORC1 inhibitor and stimulator, respectively), and torin 1 or PIP3 (mTORC2 inhibitor and stimulator, respectively). TNF-±, IL-6, IL-12, IL-4, and IL-10 levels will be determined in the medium. Statistical analysis will be performed using the softwares SPSS v. 24and GraphPad Prism v.7.0. Data normality will be assessed by Shapiro-Wilk test. Generalized estimating equation (GEE) and generalized linear models (GLM) will be used for within-between groups comparisons. In all analysis, the significance will be established at p < 0.05.

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