In flies, this anti-obesity effect of decreased IIS appears independent of dfoxo. Interestingly, it has recently been appreciated that, in vivo, insulin can regulate metabolic functions in the mouse liver in the absence of FoxO1 and its upstream insulin-responsive kinases Akt1 and Akt2 [26]. The gene discussed is FOXO1; the disease is obesity due to melanocortin 4 receptor deficiency.