Rodent model studies of estrogen deficiencies as well as clinical studies in women with polycystic ovarian syndrome, postmenopausal women, and aromatase-deficient men (42, 43) demonstrate protective effects of estrogen on metabolic function by reducing proinflammatory cytokines and maintaining insulin sensitivity during obesity (12, 20, 44, 45). This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.