Macrophage infiltration into adipose tissue: initiation, propagation and remodeling

Abstract

It has long been known that adipose tissue in obesity is in a heightened state of inflammation. Recently, our understanding of this has been transformed by the knowledge that immune cells such as macrophages and T cells can infiltrate adipose tissue and are responsible for the majority of inflammatory cytokine production. These seminal findings have opened up a new area in biology that is garnering the interest of scientists involved in research relating to cell motility, inflammation, obesity, physiology, diabetes and cardiovascular disease. Some important general questions relevant to this field are: how are macrophages recruited to adipose tissue in obesity? What are the physiological consequences of macrophage-adipocyte interactions? Do these inflammatory macrophages contribute to pathophysiological conditions associated with obesity, such as insulin resistance, dyslipidemia, diabetes and cardiovascular disease? This review focuses on the first of these important questions. Keywords activation; adipose tissue; chemokines; crown-like structures; hypoxia; inflammation; insulin resistance; leptin; lymphocytes; macrophages During the past two decades, the complex nature of adipose tissue (AT) has become an area of intense investigation. This is in part due to the growing worldwide obesity epidemic, and in part to the identification of leptin as an adipokine secreted from AT. Since the discovery of leptin, many other adipokines, such as adiponectin, resistin, visfatin and omentin, have also been identified. These discoveries have led to the first revolution in the field of AT biology, the identification of AT as an endocrine organ. More recently, it has been discovered that not only adipocytes, but also immune cells, such as macrophages [1,2] and T lymphocytes [3][4][5], reside in AT, and that these cells may induce insulin resistance by promoting a proinflammatory milieu within the AT. This discovery has led to the second revolution in the field of AT biology,

Functional Heterogeneity of CD11c-positive Adipose Tissue Macrophages in Diet-induced Obese Mice

“…The increase in ATM content in the epididymal fat pad was comparable with accumulation of ATMs in other visceral depots such as mesenteric and retroperitoneal fat. Interestingly, as previously noted (26,27), ATM content in subcutaneous adipose tissue did not increase nearly as much as in the visceral fat (supplemental Fig. 2).…”

Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women

“…39,40 It is known that the nature of macrophages is heterogeneous and their phenotype can be modified in various conditions. 26,41,42 It is therefore important to determine not only the total number of macrophages but also their phenotype in AT. From a wide range of macrophage polarization states, the most frequently described have been M1 as 'classically activated' releasing pro-inflammatory cytokines and M2 as 'alternatively activated' producing anti-inflammatory cytokines.…”

Overexpression of TNF-α converting enzyme promotes adipose tissue inflammation and fibrosis induced by high fat diet

“…Since the feature of adipose tissue inflammation in obesity has been shown as a low-grade macrophage infiltration with circulating macrophage-related cytokines and chemokines (Surmi and Hasty, 2008), the serum concentrations of IFN-γ, IL-1β, and MCP-1 were determined. At 13 weeks after the beginning of the diet, the serum concentrations of these molecules were higher in Tg-HFD mice than those in other groups of mice (Figure 2).…”