The Role of the Immune System in Obesity and Insulin Resistance
Figure 1
Role of the immune system in lean versus obese adipose tissue. In lean adipose tissue, T-helper type 2 (TH2) cells produce anti-inflammatory cytokines such as interleukin (IL)-4, 10, and 13 which promote alternatively activated M2 macrophage polarization. M2 polarization is also induced by regulatory T cells (Tregs) and eosinophils via IL-4. M2 macrophages secrete other anti-inflammatory signals such as IL-10 which maintain insulin sensitivity within lean adipose tissue. Conversely, TH1 type cytokines such as interferon (IFN)-γ stimulate M1 macrophage polarization in obese adipose tissue. Other immune cells are also increased in obese adipose tissue which contribute to insulin resistance including mast cells, B cells, and immunoglobulins (Igs). CD8(+) T cells promote ATM accumulation and proinflammatory gene expression and are also increased as well. Macrophages are not homogenously distributed throughout obese adipose tissue but rather aggregated around dead adipocytes forming crown-like structures (CLS). M1 macrophages are proinflammatory, secreting cytokines such as TNF-α and IL-1β. Macrophages are bone-marrow-derived myeloid cells hence both M1 and M2 macrophages express the myeloid cell surface markers F4/80 and CD11b. However, only the M1 population expresses the marker CD11c.
