(A) In the setting of obesity, a generally antiinflammatory immune milieu is replaced by proinflammatory immune cells, like “M1-like” macrophages, CD8⁺ T cells, and others. These cells secrete cytokines that reduce insulin action in the adipocyte and, eventually, systemically. (B) Critical observations that support the paradigm in A and whether they have been shown in mice and humans. IR, insulin resistance.