Inflammatory Mediators and Insulin Resistance in Obesity: Role of Nuclear Receptor Signaling in Macrophages

Figure 1

Cytokine release by adipose tissue macrophages contributes to insulin resistance. Free fatty acids (FFAs) released from visceral adipose tissue (VAT) promote polarization toward the M1 phenotype through activation of Toll-like receptors (TLRs), and also impair insulin secretion and action. Differentiation to the M1 phenotype is inhibited by PPAR$\gamma$ signaling, and activation of PPAR$\gamma$ or PPARδ, in response to IL-4, promotes polarization toward the M2 phenotype. IL-13 is also suggested to be involved in the M2 phenotype switch. Inflammatory monocytes migrating into VAT can also differentiate into M1 macrophages. Inflammatory mediators produced by M1 ATMs alter insulin responsiveness. CCR2: chemokine receptor-2, TNFα: tumor necrosis factor, iNOS: inducible nitric oxide synthase, IL-6: interleukin-6, TGF-β: transforming growth factor beta, IL-10: interleukin-10, Ym1: secretory chitinase protein-1, MCP-1: monocyte chemoattractant protein-1 (MCP-1).