TNF and Insulin resistance: Moreover, TNF-α plays a pathological role by (1) Inhibiting insulin signaling in muscle and adipose tissues, thereby contributing to insulin resistance; (2) Promoting a low-grade inflammatory state through continuous activation of macrophages in adipose tissue; and (3) Stimulating the release of other chronic cytokines, perpetuating the inflammatory cycle [2,3,61,62] (Figure 2).