Persistent inflammation is the common denominator and unifying mechanism of several common diseases, such as cardiometabolic disorders. Obesity-related metabolic-inflammatory conditions, including insulin resistance, diabetes and non-alcoholic fatty liver disease (NAFLD) lead to substantial morbidity and mortality and are therefore major health burdens in the western society, especially because obesity has evolved into a world epidemic. Inflammation has been recognized as an important player in the context of these diseases. Specifically, obesity-associated inflammation of metabolic organs, such as the adipose tissue or the liver, contributes to metabolic dysfunction and systemic inflammation, and thereby to progression of metabolic-inflammatory diseases. However, the mechanisms underlying inflammation of metabolic organs are not well understood. The major objective of this project is therefore to understand principles and mechanisms leading to sustained inflammation. A particular focus is inflammation of metabolic organs (adipose tissue and liver) in the context of obesity-related insulin resistance and inflammation, as well as NAFLD development and progression. Inflammation is triggered by tissue accumulation of innate immune cells, such as neutrophils and inflammatory monocytes/macrophages. Recruitment of these leukocytes is therefore a major mechanism that initiates inflammation. Whereas resolution of inflammation, involving several processes, including clearance of dead cells by macrophages, is functional in acute inflammation, resolution fails in chronic inflammatory conditions. In the latter case, failed resolution of inflammation is also linked with retention and sustained activation of innate immune cells in the tissue and contributes to perpetuation of inflammation and loss of tissue homeostasis. In other words, chronic inflammation is associated with persistent retention of inflammatory cells within the tissue, which may involve interactions of inflammatory cells with parenchymal cells, as well as dysfunctional resolution of inflammation. We therefore pursue the major objective of this project, which is to understand the mechanisms leading to sustained inflammation by (i) characterizing mechanisms for chronicity of inflammation particularly in the context of metabolic disease, including novel processes mediating inflammatory cell retention in metabolic organs and thus perpetuation of inflammation, and by (ii) studying resolution of inflammation in metabolic-inflammatory disease. In the latter approach, we also utilize models of acute inflammation, which is capable to resolve, in order to understand resolution principles.