INS and Hyperinsulinemia: While the effect of MLN4924 maybe global48, mimicking hyperinsulinemia via chronic administration of long-acting insulin (Glargine®) reverses the inhibitory effect of MLN4924 on HFD-induced weight gain (Fig. S5d), suggesting that MLN4924 inhibits diet-induced obesity at least in part via inhibiting insulin hypersecretion.