Copper, increased by obesity, could directly raise the levels of reactive oxygen species (ROS) and reduced the activities of antioxidant enzymes, further activating the microglial ROS/nuclear factor-kappa B (NF-κB) pathway to secrete inflammatory products, leading to neuroinflammatory response and neuronal apoptosis [81, 82], thereby inducing depression [83]. Here, NFKB1 is linked to obesity due to melanocortin 4 receptor deficiency.