A defective FGF21 receptor complex in adipose tissue of Tg mice might lead to the lack of an improvement in parameters of glucose homeostasis following rmuFGF21 treatment. To investigate this possibility, we analyzed gene expression of Fgf21, Klb and Fgfr1c in the adipose tissue of WT and Tg mice (Figure 2A). Interestingly we found that Fgf21 was overexpressed approximately 9-fold in Tg vs. WT adipose (consistent with Figure S1C). This was associated with a similar increase in circulating FGF21 levels 1.86±0.31 ng/mL vs. 0.31±0.04 ng/mL in Tg vs. WT, respectively (P<0.01). As receptor downregulation could account for an increase in Fgf21 expression, the expression of the Klb and Fgfr1c components of the FGF21 receptor complex were also measured, but we failed to detect a difference in their expression (Figure 2A), however we had previously observed a small decrease in Fgfr1c in WAT (consistent with Figure S1C). To rule-out any post-translational downregulation of β-klotho, we performed immunoblot analyses and failed to find any differences in β-klotho protein levels of Tg vs. WT mice (Figure 2B). Treatment with rmuFGF21 did not significantly alter the expression of these genes.
