TNF and obesity due to melanocortin 4 receptor deficiency: During obesity, signals mostly from hypertrophic and dysfunctional adipocytes drive M2-to-M1 transition of AT macrophages, which then become a major source of pro-inflammatory factors, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, thus amplifying adipocyte dysfunction and recruiting and activating more pro-inflammatory cells in a vicious cycle, and ultimately contributing to local and systemic chronic low-grade inflammation and insulin resistance [1].