In various metabolic contexts associated with pro-inflammatory processes, such as obesity, insulin resistance, and T2D, it has been identified that increases in cytokines, changes in the intestinal microbiota, as well as damage to the intestinal epithelium, bacterial translocation, and metabolic endotoxemia with elevated LPS, can affect insulin signaling in different tissues through an inflammatory process involving key kinases such as IKKβ, JNK, PKC, and JAK/STAT, all of which play crucial roles in promoting insulin resistance. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.