Figure 8. Metformin inhibits FXR target gene induction by TCA and BA excretion in vivo.

(A) FXR target gene expression in liver. C57BL/6 mice were treated with 0.5% TCA and/or metformin (ca. 50–80 mpk/d). FXR target gene expression was monitored by RT-qPCR, and results are expressed relative to control samples (chow diet) arbitrarily set to 1. (B) Biometric and plasma biochemical parameters. (C) BA content in plasma, gallbladder, and feces. BA content was assayed as described in Methods. Results are expressed as in C. (D) Phosphorylation state of FXR in mouse livers. Bar graph represents the densitometric quantification of Western blot analysis (see Supplemental Figure 16), which is expressed as values of the phospho signal normalized to that of total FXR, relative to the chow diet signal. which was arbitrarily set to 1. *P < 0.05; **P < 0.01; ***P < 0.005.