Evaluation of mTORC2 role as a mediator of LPS inflammatory and metabolic actions in liver using a perfusable liver-on-a-chip system

• Grant number: 24/06344-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: July 25, 2024
• End date: July 24, 2025
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: William Tadeu Lara Festuccia
• Grantee: Bianca Franco Leonardi
• Supervisor: Frank Tacke
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Charité - Universitätsmedizin Berlin, Germany
• Associated to the scholarship: 21/14419-0 - Involvement of hepatocyte and macrophage Rictor/mTORC2 as mediator of LPS metabolic and inflammatory actions in the liver., BP.PD

Abstract

Despite recent advances, the molecular mechanisms and signaling pathways that contribute to metabolic dysfunction-associated steatotic liver disease (MASLD) onset and progression are not completely understood. Several pieces of evidence indicate that elevated serum lipopolysaccharides (LPS) levels (endotoxemia) due to intestinal dysbiosis play a major role in MASLD development exacerbating lipid deposition, inflammation, oxidative stress, mitochondrial dysfunction, among other phenotypes commonly found in this disease. Therefore, in the current proposal, we will investigate the involvement of mTORC2 as a mediator of LPS actions in liver by using an innovative perfusable liver-on-a-chip system. This system will allow us to investigate the contributions of mTORC2 and specific cell populations namely Kupffer, monocyte-derived macrophages, stellate and endothelial cells to LPS signaling in hepatocytes expanding our understanding about liver LPS signaling, mTORC2 and regulation of metabolism, inflammation and fibrosis.