Obesity-associated adipose inflammation. In the lean state, immune cells in adipose tissues (primarily resident M2-like macrophages together with T regulatory (Treg) cells and eosinophils) synthesize IL-10, IL-4, and IL-13 and help to maintain an anti-inflammatory environment that contributes to the insulin-sensitive state. Obesity drives a shift in the number and phenotype of immune cells.^74,75  Monocytes are recruited from the blood into the obese adipose tissue, where they become M1 polarized and produce proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, which contribute to insulin resistance. Other changes contributing to the proinflammatory state include decreased numbers of eosinophils and Tregs, and increased numbers of neutrophils, B cells, mast cells, and interferon γ–producing Th1 and CD8+ T cells. The proinflammatory cytokines and chemokines act in autocrine, paracrine, and endocrine manners to promote inflammation and insulin resistance in adipose and other target tissues.