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.

Figure 1. Stages of macrophage infiltration into adipose tissue obesity

During weight gain, macrophages are recruited to the expanding adipose tissue (AT) bed. Factors that initiate this process are thought to be derived from the adipocytes or capillary endothelial cells within AT and include adipocyte secretion of leptin, hypoxia, adipocyte cell death and initial infiltration of other immune cells, such as neutrophils and T cells. Adipose tissue macrophages (ATMs) are highly inflammatory, secreting cytokines such as TNF-α, and likely contribute to propagation of the recruitment of additional macrophages by secreting chemokines such as MCP-1 and MIP-1α. A dramatic increase in ATMs results in the formation of CLS that surround the dead adipocytes. These macrophages appear to contribute to remodeling of AT, during which fewer CLS are present and AT expansion may occur via hyperplasia more than hypertrophy. In addition, a repolarization from an M1 toward an M2 phenotype may occur. CLS: Crown-like structures; MCP-1: Monocyte chemotactic protein-1; MIP-1α: Macrophage inflammatory protein 1α.