Notably, the plasma levels of insulin and leptin, an adipokine that positively correlates to obesity and fat mass (Considine et al., 1996), were markedly elevated in both chow- and HFD-fed mice, while as an important adipose-derived hormone, adiponectin, the level of which is closely associated with insulin resistance and negatively correlated with adiposity (Yamauchi et al., 2001), was decreased by 36 and 32% in chow- and HFD-fed AKO mice, respectively (Table 1). This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.