These effects of estrogen may explain some of the findings in genome-wide association studies with more than 224,000 individuals (65), showing that metabolic changes are likely involved in the sexual dimorphism of obesity and fat distribution, implicating mechanisms via differential control of adipogenesis and insulin resistance between sexes (1, 65, 66). The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.