Dietary fat and adipocyte-macrophage interaction

肥胖导致脂肪组织的慢性低度炎症，其特征是组织环境中促炎分子数量增加和激活免疫细胞的募集。募集到外周组织的单核细胞成为常驻巨噬细胞，促进局部炎症和胰岛素抵抗的发展。由于能量输入不平衡导致肥胖增加脂肪组织质量，与促炎反应相关，白色脂肪组织功能受损。这涉及到全身能量稳态的调节，即以甘油三酯的形式储存多余的能量，并根据需要将其转化为游离脂肪酸和甘油，以及作为内分泌器官的功能。然而，巨噬细胞可以表现出显著的表型异质性，从而发挥截然不同的作用。它们可以被经典地分为三大类：（M0）非极化巨噬细胞，（M1）经典活化的巨噬细胞，或（M2）交替活化的巨噬细胞。在肥胖中，M1/ m2样巨噬细胞比例失衡，促炎M1样巨噬细胞增强，抗炎m2样巨噬细胞下调。多年来，w-3多不饱和脂肪酸的抗炎和有益作用已经得到证实。本项目的目的是了解w-3 PUFAs是否通过影响巨噬细胞极化来发挥其抗炎功能。我们计划系统地研究脂肪细胞巨噬细胞相互作用和脂肪细胞信号传导对脂肪细胞脂肪成分的依赖性。该项目将重点关注脂肪细胞积累各种脂肪酸的能力，以及依赖于脂肪细胞脂肪酸饱和状态对细胞（氧化还原）信号变化的反应。信号事件对巨噬细胞的作用以及巨噬细胞分化为M1、M2和其他类型将被研究。

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.