Intriguingly, prolonged HFD not only aggravated the activation of p70S6K signaling but also led to an elevation of PDZ-RhoGEF protein levels in all peripheral insulin-targeted tissues, EWAT, skeletal muscle (EDL), and liver (Figure 7D), suggesting that high levels of PDZ-RhoGEF accompany HFD-induced insulin resistance in wild type animals. Here, INS is linked to Insulin resistance.