Macrophage recruitment in obese adipose tissue

Abstract

Obesity is characterized as a chronic state of low-grade inflammation with progressive immune cell infiltration into adipose tissues. Adipose tissue macrophages play critical roles in the establishment of the chronic inflammatory state and metabolic dysfunctions. The novel discovery that pro-inflammatory macrophages are recruited to obese adipose tissue prompted an increased interest in the interplay between immune cells and metabolism. Since this discovery, many works have been published investigating the factors that lead to macrophage recruitment, the phenotypic change of adipose tissue macrophages, and metabolic dysfunctions. Adipokines and chemokines are key mediators that play crucial roles in crosstalk between adipocytes and macrophages and in regulating the adipose tissue inflammation. In the present review, we discuss the obesity-mediated adipose tissue remodelling, and particularly, the role of adipokines/chemokines in macrophage recruitment to obese adipose tissue. This review provides new insights into the physiological role of these factors and identifies a potential therapeutic target for obesity and associated disorders.

Keywords: Adipokine; chemokine; macrophage; obesity.

Figure 1. The role of crosstalk between adipocytes and macrophages in macrophage recruitment

(1) obese adipocytes expand their sizes and break the balance between the levels of pro-inflammatory and anti-inflammatory adipokines; (2) obesity causes an increase in local concentration of extracellular fatty acids through upregulation of basal lipolysis, which involves multiple adipokines as well as other adipose tissue-derived proteins; free fatty acids can bind macrophages either directly via CD36 or indirectly via the ligand of Fetuin-A; (3) adipocytes communicate with macrophages via pro-inflammatory adipokines in a paracrine pathway; these adipokines bind macrophages via TLR4 or CCR2; (4) upon binding to fatty acids and adipokines, the resident macrophages can be activated and then transduce the signal into nucleus where NF-κB is activated, thereby contributing to the release of pro-inflammatory chemokines such as MCP-1; (5) adipocytes also secrete amyloid A that activates the adhesion molecules, promoting the monocyte trafficking; (6) monocytes move toward the higher concentration of MCP-1 via binding to CCR2, which is the process known as chemotaxis; (7) matured monocytes contribute to macrophage accumulation within AT; (8) MCP-1-driven in situ proliferation of macrophages also contributes to macrophage accumulation; macrophages encircle the dead adipocytes caused by obesity, forming crown-like structure. TLR: toll-like receptor; CD36: cluster of differentiation 36; MCP-1: monocyte chemotactic protein-1; CCR2: C-C chemokine receptor type 2; NF-κB: nuclear factor-κB.