Recently, specific silencing of ER-α in the hypothalamus of female rodents has been shown to lead to obesity, hyperphagia, and reduced energy expenditure, indicating that ER-α in hypothalamic neurons plays an essential role in the control of energy balance and the maintenance of normal body weight (Musatov et al. 2007). Here, ESR1 is linked to obesity due to melanocortin 4 receptor deficiency.