Characterization of lipid metabolism alterations in experimental Sepsis and their contribution to neuroinflammation postsepsis

• Grant number: 24/18351-9
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: March 10, 2025
• End date: April 29, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Patricia Torres Bozza
• Grantee: Armando da Silva Pires
• Host Institution: FUND OSVALDO CRUZ RIO JANEIRO/FIOCRUZ

Abstract

Sepsis can be defined as a life-threatening dysregulated inflammatory and metabolic response of the host to a severe infection with organ dysfunction (1). This syndrome affects 19 million people a year and represents 20% of all deaths registered in the world. Mortality among septic patients who developed multiple organ failure ranges from 11% to 54% in pediatric sepsis, while in adults it is around 44% to 50% - making sepsis the leading cause of hospitalization and death in ICUs (2). Studies by our group, and others, have indicated an important role of alterations in lipid metabolism and lipid droplets in the host dysregulated immunoinflammatory response to infection that contributes to tissue damage and organ dysfunction (3-5). We hypothesize that alterations in lipid metabolism and the accumulation of lipid droplets in different cells and tissues contribute to the amplification mechanisms of tissue damage, organ dysfunction, and long-term consequences associated with sepsis. In this project we will characterize: i. alterations in lipid metabolism and inflammatory response in the brain of mice submitted to experimental sepsis; ii. the impact of lipid metabolism on sepsis through the use of the DGAT-1 enzyme inhibitor in an experimental sepsis model; III. The consequences of changes in lipid metabolism in neuroinflammation after sepsis. A better understanding of the importance of lipid metabolism in the pathophysiology of sepsis may contribute to the identification of biomarkers and therapeutic targets.