We used STF-083010 (STF), a member of hydroxy-aryl-aldehyde class of IRE1α RNase inhibitors that engage the RNase-active site of IRE1a with high affinity and specificity by exploiting a shallow complementary pocket through pi-stacking interactions with His910 and Phe889 and an essential Schiff base interaction between the aldehyde moiety of the inhibitor and the side chain amino group of Lys907 (Sanches, Duffy et al. 2014), to treat diet-induced obesity (DIO) mice with established insulin resistance. Here, ERN1 is linked to Insulin resistance.