In lean, insulin-sensitive states, ATMs are polarized toward an M2 state with IL-10 and arginase expression. Early during HFD treatment, adipocytes undergo hypertrophy, releasing chemokines that induce recruitment of M1-polarized ATMs with low IL-10 expression and increased iNOS and TNF-α production. In these early stages of mild obesity with retained insulin sensitivity, M2-polarized resident ATMs are able to partially protect adipocytes from these inflammatory factors and may block M1 polarization. With increased adiposity, recruited CCR2+ ATMs form crownlike structures (CLS) and overwhelm the protective effects of M2 macrophages, leading to a dominant role for TNF-α and iNOS. These factors generate insulin resistance in adipocytes, activate JNK and NF-κB, alter adipokine secretion, and lead to excess circulating levels of free fatty acids due to adipocyte lipolysis and impaired lipogenesis.