normalized (Figure S4C–D), and the steatosis in Tg mice had been reversed (Figure S4E vs. S4F). We observed that every transplanted fat pad was viable and had low grade inflammatory cell infiltrate (Figure S4G). Based on these data we investigated whether WAT transplantation could restore FGF21 efficacy. Immediately following implantation or sham surgery, the group average fat mass was increased from 1.4 g to 3.2 g in Tg transplanted (Tg–tx) mice (Figure 4A). At the completion of the study we measured leptin and found minimal increases in the Tg transplant mice in contrast to our pilot data (Figure S4B) and suspect that this may be related to differences in the 2 study designs; the pilot mice were implanted and allowed to fully heal, whereas the mice in this study were implanted, handled twice daily and tested for 2 weeks following transplantation. Nonetheless the transplantation methodology was successful in this study for several reasons, namely, plasma glucose, NEFAs, plasma FGF21 and 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
