liver weights were all lower in Tg–tx mice compared to Tg-sham mice (Figures S5A–D). Following the recovery period, WT sham, Tg sham and Tg–tx mice were treated with either vehicle or 10 mg/kg rmuFGF21. In mice treated with rmuFGF21, body weight was reduced in WT sham mice but not in Tg sham mice (Figure 4C–D), whereas body weight was significantly reduced in Tg–tx mice injected with rmuFGF21 compared to vehicle Tg–tx mice (Figure 4E). Glucose tolerance was improved in WT sham mice treated with muFGF21, but not in Tg sham mice also treated with rmuFGF21 when compared to vehicle-treated mice (Figures 4F–G). Importantly, Tg–tx mice treated with rmuFGF21 exhibited improved glucose tolerance vs. Tg–tx mice treated with vehicle (Figure 4H). These data strongly support a critical role of adipose tissue in eliciting the pharmacologic response of FGF21 on glucose homeostasis.