TNF and obesity due to melanocortin 4 receptor deficiency: In the context of obesity, ATM was activated into proinfammatory M1 macrophages in AT, which produces a variety of proinflammatory cytokines such as tumor necrosis factor alpha (TNFa), macrophage-colony-stimulating factor (MCSF), retinol binding protein 4 (RBP-4), etc., directly inhibiting insulin sensitivity in skeletal muscle [73,74].