In this sense, activation of FoxO1 in response to the HFD was directly related to down-regulation of IRS1 activity, decreased AKT signaling, and insulin resistance, suggesting that FoxO1 might be a key step in the development of DCM preventing cardiac dysfunction by restoring insulin responsiveness (Battiprolu et al., 2012; Figure 1B). Here, FOXO1 is linked to Insulin resistance.