Figure 3.

Obesity results in recruitment of macrophages into adipose tissue, which promotes adipose tissue inflammation and insulin resistance. Obesity results in increased levels of circulating saturated fatty acids, which activate Toll-like receptors 2/4 (TLR2/4) to promote classical activation of adipose tissue macrophages. Secretion of inflammatory cytokines, such as IL-1β and TNF-α, by adipose tissue macrophages inhibits insulin action in adipocytes. Moreover, activation of the NLRP3-containing inflammasomes, potentially by ceramides, augments the release IL-1β by classically activated macrophages. Cross talk between adipocytes and adipose tissue macrophages perpetuates these inflammatory cascades via release of chemokines, cytokines, and fatty acids. Ccl2 and osteopontin (OPN) are two chemoattractants implicated in the recruitment of Ly6C⁺CCR2⁺ inflammatory monocytes, which differentiate into classically activated adipose tissue macrophages. CD5-like antigen (CD5L), a peptide released by macrophages that is incorporated into adipocytes via CD36-mediated endocytosis, potentiates lipolysis of triglycerides in adipocytes. This establishes a feed-forward loop in which the released fatty acids induce chemokine expression, potentiating monocyte and macrophage recruitment into adipose tissue. By inhibiting the IL-4- and PPARγ-driven program of alternative activation, mineralocorticoid (MR) signaling contributes to classical activation of adipose tissue macrophages. (This figure is from Chawla et al. 2011; reprinted, with express permission, from the author.)