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Obesity is associated with increased macrophage infiltration of adipose tissue, and these macrophages may be an important component of the chronic inflammatory response playing a crucial role in the development of insulin resistance. This prompts the question as to how macrophages infiltrate obese adipose tissue. In this issue of the JCI, Weisberg et al. show the importance of C-C motif chemokine receptor 2 (CCR2) in macrophage recruitment to adipose tissue and the development of obesity and its complications (see the related article beginning on page 115).
Nonstandard abbreviations used: ATM, adipose tissue macrophage; CCL2, C-C motif chemokine ligand 2; CCR2, C-C motif chemokine receptor 2; HFD, high-fat diet.
Insulin resistance, inflammation, and macrophages
Insulin resistance is a characteristic feature of most patients with type 2 diabetes melIitus, simple obesity, polycystic ovarian syndrome, and impaired glucose tolerance, as well as other disorders (1). There are also a number of other manifestations associated with insulin resistance, and this constellation of abnormalities is generally described by the term "syndrome X" or "metabolic syndrome" (1). Decreased insulin sensitivity is the central feature of this syndrome, and other components include obesity, hypertension, dyslipidemia, and hyperuricemia (1). In recent years, the general concept has emerged that chronic activation of the proinflammatory pathway can be a mechanism for insulin resistance (2). Various studies have implicated chronic activation of the NF-κB proinflammatory pathway and/or JNK1 as underlying mechanisms, and most of these studies have focused on activation of this pathway within insulin target tissues (adipose, liver, and muscle) as an etiologic mechanism (2). The adipocyte has emerged as an important player in this process, since this cell type can be the source of a large number of cytokines/chemokines (TNF-α, IL-6, IL-1, monocyte chemoattractant protein-1, etc.) and adipokines (leptin, adiponectin, and resistin), and all of these molecules can exert potential negative or positive effects on insulin sensitivity in an endocrine or paracrine fashion (Figure 1A) (3). While there is no question that the inflammatory pathway becomes activated in adipose tissue in various insulin-resistant states, and that this has deleterious effects on insulin action in adipocytes, the total contribution of adipose tissue as a systemic source of these circulating cytokines/chemokines is still unclear. In this regard, recent attention has focused on the potential role...