IRS1 and obesity due to melanocortin 4 receptor deficiency: In our study, the similar results with increased expression levels of the proteins associated with the signal pathways of insulin resistance such as JNK/IRS-1/PI3K/Akt in the hippocampal tissues of the obese mice were observed, and the swimming intervention rescued the abnormal expression of these proteins (Figure 5), further suggesting impaired learning and memory capacity due to the insulin resistance from high-fat diets, and alleviated the obesity state and recovered insulin resistance for enhancing learning and memory capacity upon regular exercise intervention.