Lymphocyte metabolic alterations in obesity

• Grant number: 20/14236-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2021
• End date: December 31, 2022
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Renata Gorjao
• Grantee: Maria Janaina Leite de Araújo
• Host Institution: Pró-Reitoria de Pós-Graduação e Pesquisa. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil

Abstract

Obesity is characterized by increased adipose tissue that causes more secretion of pro-inflammatory adipokines. This increase of adipocytes and proinflammatory factors leads to chronic inflammation that is associated with an imbalance of the immune system and the appearance of diseases. The increase in plasma leptin in obesity results in the polarization of naive lymphocytes (Th0) to Th1 cells accompanied by inhibition of regulatory T cells (Treg). Lymphocyte differentiation is associated with important metabolic changes. The flow of the glycolytic pathway correlates with the differentiation of Th0 cells to Th1 and Th17, which exhibit inflammatory activity. The inhibition of the glycolytic pathway blocks this process and promotes differentiation to Treg cells. We hypothesize that, in obese patients, lymphocyte polarization to the Th1 and Th17 profile occurs, accompanied by an increase in the activity of the glycolytic pathway. Initially, 20 men classified as obese aged between 18 and 50 years will be recruited through the analysis of the body mass index (BMI), which should be higher than 30 kg / m2. In parallel, we will recruit 20 eutrophic men (BMI <25 Kg / m2). Body composition assessments will be carried out to better characterize the group. The following parameters will be evaluated: Th1, Th2, and Th17 profile; analysis of GLUT1 mRNA expression and enzymes involved with beta-oxidation of fatty acids by real-time PCR; analysis of glucose consumption by lymphocytes in culture by flow cytometry; evaluation of lactate production and hexokinase activity, citrate synthase, glucose 6-phosphate dehydrogenase (G6PDH) and pyruvate dehydrogenase by spectrophotometry. This study will allow determining the metabolic changes in the lymphocyte differentiation process that may be related to the inflammatory profile observed in obese individuals.