Macrophages are evolutionary ancient cells that are critical for maintaining tissue integrity by performing catabolic and anabolic reactions in tissues, and the disturbance of macrophage function can promote disease. Recent data indicate that macrophages use different metabolic programs to perform individual effector functions in vitro. However, the role of metabolic signals and the cellular metabolism for macrophage function are multifaceted, complex, and underexplored in vivo. In the first funding period, we have comparatively characterized the metabolic profile of different tissue-resident macrophage populations and how they contribute to disease. A comprehensive understanding of the immunometabolic functions of macrophages and their communication with tissues in vivo will be of critical importance in determining how macrophages maintain tissue integrity and how they contribute to tissue dysfunction in diseases such as obesity, type 2 diabetes, colitis, cancer, cachexia, or liver diseases. The goal of the F83 SFB IMMUNOMETABOLISM is to reveal the in vivo relevance of metabolic reprogramming in macrophages for tissue function. We want to discover novel therapeutic approaches that target the metabolism and the metabolic signals of macrophages in human disease.