Modulation by the fatty acid profile of inflammatory macrophage activity in cancer cachexia: consequences on cell function

• Grant number: 16/09988-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: September 01, 2016
• End date: February 28, 2017
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Marilia Cerqueira Leite Seelaender
• Grantee: Katrin Radloff
• Supervisor: Gerhard Puschel
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Potsdam, Germany
• Associated to the scholarship: 13/25207-7 - Is inflammation resolution failing in adipose tissue of cachectic patients?, BP.DD

Abstract

Cancer cachexia is a syndrome with severe and fast involuntary weight loss. It affects around 80% of patients with advanced cancer and is the direct cause of death of a large proportion of these. Recent studies have shown that inflammatory mediators are active players in the development of cachexia, considered nowadays a chronic inflammatory condition. The white adipose tissue is a contributor to inflammation as it suffers morphological reorganization and marked lipolysis, releasing free fatty acids (FA), which accentuate the production of pro-inflammatory cytokines through the activation of pro-inflammatory signalling pathways and recruitment of macrophages to the tissue. In plasma of cachectic cancer patients our group found that saturated FA such as palmitic and stearic acid were increased whereas the percentages of poly-unsaturated Dihomo-³-linolenic acid and ±-Linolenic acid was lower. This project will investigate the effects of fatty acids (FA) and prostaglandins that are altered in cachectic gastrointestinal cancer patients on the macrophage cell line U937. We aim to identify which inflammatory pathways and secretory proteins of macrophages are modulated by the microenvironment. At the same time, the influence of inflammatory factors upon enzymes involved in FA metabolism will be analysed. Immune cells namely monocytes, T-cells and macrophages express many enzymes converting FA to lipid mediators and carry receptors that are activated by FA and their products. Thus, resident and infiltrating immune cells into the adipose tissue are not only affected by FA and lipid mediators, yet presumably also play an important role in mediating the anti- and pro-inflammatory input within the tissue. (AU)