(A) Western blot analysis of total and phosphorylated FRS2α, ERK1/2, CREB, Akt, and FOXO1 in liver lysates from individual overnight fasted wild-type (WT) and FGFR4-knockout (KO) mice 30 min after treatment with vehicle or FGF19. β-Actin served as a loading control. (B–E) ChIP analysis of the cyclic AMP response elements (CRE) in the Pgc1α, G6pase, and Pepck promoters using CREB, CBP and PGC-1α antibodies as indicated and pooled liver lysates (three repeats/pool; n = 4/pool of each group). For (B), mice were administered saline or FGF19 for 1 hr and fasted during the treatment period. For (C–E), mice were injected with control or FGF15-expressing adenovirus for 3 days and killed after an overnight fast. (F) Images of luciferase activity in mice infected with a CRE-luciferase reporter (Ad-CRE-luc) or control adenovirus and subsequently treated with vehicle or FGF19 for 6 hr. Mice were fasted during the treatment period. (G) Quantified luciferase activity normalized to the number of virus particles per liver (n = 6/group). All data are presented as mean ± SEM (c, P< 0.005). See also Fig. S3.