Obesity-induced oxidative stress may drive sustained activation of the Na/K-ATPase signaling pathway (the phosphorylation of ERK1/2, Figure 4A), ultimately leading to the pathway desensitization, and down-regulation of the MAPK signaling pathway may be an adaptive response to this phenomenon, which is one of the underlying mechanisms contributing to the impaired sodium excretion observed in obese mice under high salt intake. Here, MAPK3 is linked to obesity due to melanocortin 4 receptor deficiency.