Dietary fat and adipocyte-macrophage interaction

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Obesity leads to a chronic low-grade inflammation of the adipose tissue characterized by an elevated number of pro-inflammatory molecules in tissue environment and the recruitment of activated immune cells. Monocytes recruited to peripheral tissues become resident macrophages and contribute to the development of local inflammation and insulin resistance. As obesity increased adipose tissue mass, resulting from unbalanced energy inputs, is associated with pro-inflammatory responses, the white adipose tissue function is impaired. This relates to the regulation of whole-body energy homeostasis, i.e. storing excess energy in the form of triglycerides and their conversion into free fatty acids and glycerol upon demand, as well as the function as an endocrine organ. However, macrophages can display remarkable phenotypic heterogeneity and thereby perform vastly different roles. They can be classically divided into three major subgroups: (M0) the non-polarized, (M1) the classically activated, or (M2) the alternatively activated macrophages. In obesity, an imbalance in the ratio of M1/M2-like macrophages exists, where pro-inflammatory M1-like macrophages are enhanced compared with anti-inflammatory M2-like macrophages being down-regulated. For years now, the anti-inflammatory, beneficial effects of w-3 polyunsaturated fatty acids have been demonstrated. The goal of this project is to understand whether w-3 PUFAs are developing their anti-inflammatory functions via influencing macrophage polarization. We plan systematically to investigate the adipocyte macrophage interaction and adipocyte signaling in dependence of the fat composition of the adipocytes. The project will focus on the capability of adipocytes to accumulate various fatty acids and to respond to changes in the (redox) signaling of the cells in dependence of saturation state of the adipocyte fatty acids. The role of signaling events onto the macrophages and the polarization of macrophages into M1, M2 and further types will be investigated.