ERN1 and Glucose intolerance: Male C57BL/6 J mice fed on HFD for 8 weeks gained significant glucose intolerance (Figure 1—figure supplement 1C) and were treated with STF at 10 mg/kg of BW once daily for 4 weeks (Figure 1—figure supplement 1D) via IP injection, a dose previously shown to significantly inhibits IRE1α RNase activity in vivo (Papandreou et al., 2011; Tufanli et al., 2017; Herlea-Pana et al., 2021), while still on HFD.