To evaluate the role of adipose tissue in eliciting anti-diabetic efficacy associated with FGF21 therapy, we generated mice with diminished adipose mass. These mice were intended to replicate those described by Brown and Goldstein [18], in which the mature N-terminal domain of the human SREBP1c (nSREBP1c) was overexpressed specifically in adipose tissues. Molecular characterization of the Tg mice (Figure S1A–B) demonstrated specific transgene expression in adipose tissues. Gene expression analysis of liver and adipose tissues (Figure S1C) showed multiple changes in the expression of metabolic genes. In WAT and BAT Srebp1c, Ldlr and Hmgcr were most upregulated by transgene overexpression, whereas in the liver Pparg was upregulated. In all these tissues Fgf21 was upregulated between 10–25 fold. Leptin was the most downregulated gene. The phenotype of these Tg mice when bred on the FVB background was similar to that previously reported [18]. We observed similar body weights to WT mice, but dramatically decreased fat mass and commensurate increases in lean mass (Figure S2A–C), in addition we observed hyperglycemia (Figure S2D), and mild/sporadic glucose intolerance (Figure S2E–F). Additionally, Tg mice were
