NFKB1 and obesity due to melanocortin 4 receptor deficiency: The elevated activity of NF-κB signaling in the hypothalamus of rodents on an HFD contributes to endoplasmic reticulum (ER) stress, exacerbating hypothalamic IR and accelerating the onset of both obesity and T2DM [56,59,60], as shown in Figure 2 below.