Metabolomic analysis of macrophage activation and relevance of the cross-talk between energetic metabolism and polarized gene expression (172.12)

Abstract

Abstract Immune activation rapidly and substantially enhances metabolic outputs. Macrophage activation is followed by rapid changes in nutrient flux, which also seems to be necessary for immune activation, indicating that signals produced by immune cells might directly regulate their metabolism. Macrophages respond to a variety of extracellular stimuli developing patterns of gene expression that also encompass metabolic changes linked to the activation programs and that are not fully understood. Macrophages can be activated to two opposite end-points: M1-polarization accomplished by pro-inflammatory stimuli, and M2-polarization. The study of how energetic and redox metabolism of macrophages varies in accordance with recruitment and activation (M1, M2 or mixed combinations) and how these conditions are required for the specific functions of the macrophage (oxidative burst, phagocytosis, migration and infiltration, etc) are relevant to protect organ activity and to restrict the involvement of macrophages in chronic inflammation. We have studied the metabolic profile associated with relevant activation pathways using a [1,2-<13>C]glucose tracer-based metabolomic approach and bioinformatic tools to analyze changes in isotopomer distribution and changes in main energetic metabolites under M1/M2 conditions. Our data show the existence of specific metabolic signatures depending on the activation pattern elicited by the macrophages.