动物实验,脂肪组织巨噬细胞 z-bo 2020-09-07 446

　　It is well known that chronic inflammation caused by obesity is related to the development of metabolic diseases. The results of previous studies have shown that a high-fat diet causes an increase in activated macrophages in mice, including CD11c-positive adipose tissue macrophages (ATM) that promote insulin resistance. Obesity leads to an increase in bone marrow cells produced by hematopoietic stem cells. Toll-like receptor 4 (TLR4) and downstream TRIF and MyD88-mediated signaling pathways can also regulate similar bone marrow cell production after LPS stimulation.

　　However, the role of these signaling pathways in bone marrow hyperplasia induced by high-fat diet is still unclear. Researchers at the University of Michigan recently discovered that saturated fatty acids and high-fat diets activate the TLR4 signaling pathway of hematopoietic stem cells to produce pro-inflammatory CD11c-positive bone marrow cells, thereby affecting the proliferation of bone marrow tissue. Then, he proposed a hypothesis that it can promote metabolic disorders caused by obesity. Transplanting bone marrow into Tlr4 knockout mice and wild-type mice showed that TLR4 is a key molecule required for myeloproliferation and the production of CD11c-positive adipose tissue macrophages in a high-fat diet. It is further research that MyD88 is a molecule required for the proliferation of granulocytes and monocyte progenitor cells induced by a high-fat diet, while Trif is a molecule required for the proliferation of granulocytes and macrophage progenitor cells.

　　The results showed that compared with wild-type, Tlr4 knockout, Myd88 knockout and Trif knockout mice fed a high-fat diet, TLD4 played a role in the formation of CD11c-positive adipose tissue macrophages. Trif knockout mice are produced. There are fewer adipose tissue macrophages shown than wild-type mice. In addition, the activation of TLR4 by a high-fat diet also inhibited the proliferation of macrophages, leading to the accumulation of more newly recruited adipose tissue macrophages. Results These results indicate that in the obesity model induced by a high-fat diet, TLR4 in granulocyte progenitor cells and adipose tissue and downstream signal transduction pathways through MyD88 and TRIF are activated and it indicates that it leads to polarization.

　　This study reveals the mechanism of macrophage formation in adipose tissue, and has certain importance in the development of treatments for obesity-related metabolic diseases.