A study of the effects of leptin in the function and metabolism of macrophages through mTORC1 and mTORC2 in vitro

• Grant number: 19/10876-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2019
• End date: October 31, 2021
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Pedro Manoel Mendes de Moraes Vieira
• Grantee: Juliana Silveira Prodonoff
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 15/15626-8 - Macrophages and T lymphocytes immunometabolism in metabolic and inflammatory diseases, AP.JP

Abstract

Obesity is a disease that affects millions of people worldwide. It is marked by a systemic low grade pro-inflammatory profile. Obesity-induced hyperleptinemia is a result of hypothalamic resistance to leptin. Leptin is produced by adipose tissue in response to food intake and acts on the hypothalamus, exerting control over ingestion. This adipokine also has pro-inflammatory properties. Central leptin resistance is commonly associated with increased levels of leptin in the organism, which can aggravate the systemic low grade inflammation induced by obesity. Obesity results in increased adipose tissue macrophage infiltration and the subsequent increased inflammation and insulin resistance. Thus, understanding how leptin modulates macrophages is essential. Our hypothesis is that leptin acts as a systemic nutritional status signal that, through the mTOR pathway, informs the organism and therefore macrophages on the availability of nutrients. In response, macrophages adapt their metabolism and, consequently, their functions. Our objective is to determine how leptin modulates the mTOR pathway and, subsequently, its effects on macrophage function and metabolism.