Given the sexual dimorphism in energy balance of these SF1-p110α-KO mice and the known effects of estrogens and ERα in the VMH on energy homeostasis6, 7, 8, we speculated that estrogen may be one of the hormones that drive PI3K activity in VMH neurons in females to prevent obesity. Here, ESR1 is linked to obesity due to melanocortin 4 receptor deficiency.