Role of macrophage tissue infiltration in obesity and insulin resistance

Obesity is associated with systemic chronic low-grade inflammation, a major contributor to the aetiology of insulin resistance (IR). An inflammatory response in the presence of obesity appears to be triggered by, and to reside predominantly in, adipose tissue (AT). The discovery that the AT in obese mice and humans is infiltrated with macrophages has provided a major advance in our understanding of how obesity propagates inflammation. Interestingly, AT-infiltrating macrophages exhibit a proinflammatory phenotype (classical activation) whereas macrophages residing in AT have a reparative phenotype (alternative activation). In this review, the processes involved in monocyte/macrophage recruitment into the AT, and the events underlying the activation of infiltrating and/or resident AT macrophages (ATM) are described. Also, the localized roles of ATM on AT growth, metabolism and remodelling, as well as their systemic effects in promoting IR, are revealed. Finally, the new therapeutic targets that have recently emerged, and which have the potential to modulate the recruitment and/or activation of ATM, are discussed.