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]. This evidence concerns the gene AKT2 and obesity due to melanocortin 4 receptor deficiency.