Since multifactorial domains have been hypothesized as the reasons for the epidemiological increase in obesity, 20 obese free-living Japanese females, with or without Lys109Arg polymorphism (a common polymoprhism of the leptin receptor gene associated with both insulin and glucose metabolism in women with impaired glucose metabolism and obesity along sweet preference [50]), were enrolled to complete a 12-week weight-loss program, based on energy restrictions through diet and exercise, which aimed at achieving their optimal weight. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.