From Blood Monocytes to Adipose Tissue-Resident Macrophages

TLDR

The study investigates how adipocytes influence monocyte recruitment through adipose tissue capillary endothelium in obesity. The authors isolated adipose tissue endothelial cells and resident macrophages, exposed the ECs to adipocyte‑conditioned medium, and measured adhesion molecule expression and monocyte adhesion/transmigration. They found that higher BMI is associated with more resident macrophages, and that adipocyte‑derived factors, especially leptin, upregulate endothelial adhesion molecules and promote monocyte adhesion and transmigration, linking fat mass expansion to inflammation.

Abstract

Obesity has been suggested to be a low-grade systemic inflammatory state, therefore we studied the interaction between human adipocytes and monocytes via adipose tissue (AT)-derived capillary endothelium. Cells composing the stroma-vascular fraction (SVF) of human ATs were characterized by fluorescence-activated cell sorter (FACS) analysis and two cell subsets (resident macrophages and endothelial cells [ECs]) were isolated using antibody-coupled microbeads. Media conditioned by mature adipocytes maintained in fibrin gels were applied to AT-derived ECs. Thereafter, the expression of endothelial adhesion molecules was analyzed as well as the adhesion and transmigration of human monocytes. FACS analysis showed that 11% of the SVF is composed of CD14+/CD31+ cells, characterized as resident macrophages. A positive correlation was found between the BMI and the percentage of resident macrophages, suggesting that fat tissue growth is associated with a recruitment of blood monocytes. Incubation of AT-derived ECs with adipocyte-conditioned medium resulted in the upregulation of EC adhesion molecules and the increased chemotaxis of blood monocytes, an effect mimicked by recombinant human leptin. These results indicate that adipokines, such as leptin, activate ECs, leading to an enhanced diapedesis of blood monocytes, and suggesting that fat mass growth might be linked to inflammatory processes.