IRS1 and obesity due to melanocortin 4 receptor deficiency: Chronic treatment (2–4 weeks) with rapamycin, the mTOR inhibitor, causes glucose intolerance and insulin resistance in mice [31], [32] but evodiamine appears not to be included, because administration of this compound for 2 months improved glucose tolerance and insulin resistance associated with diet-induced obesity in mice [21], in which phosphorylation levels of mTOR and IRS1 were decreased in evodiamine-treated WAT (Fig. S2 in File S1).