FIGURE 8.

FXR mediates the effects of intracerebral treatment with GW4064 on BAT. (A) Besp, (B) Shp and (I) Th mRNA expression in hypothalamus of FXR-WT and FXR-KO mice receiving vehicle solution or GW4064 by ICV injection. The values are normalized to cyclophillin or 18 s. (C) Ucp1 mRNA expression in BAT of FXR-WT and FXR-KO mice receiving vehicle solution or GW4064 by ICV injection. The values are normalized to cyclophilin. (D) UCP1 protein expression in BAT. (E) The bar graphs are the quantification of UCP1 western blots in panel (D). (F) Th mRNA expression in BAT of FXR-WT and FXR-KO mice receiving vehicle solution or GW4064 by ICV injection. The values are normalized to 18 s. (G) TH protein expression in BAT. Results are represented in the form of boxes for illustration purposes. For an experiment, all samples are processed in the same western blot. If different gels were used if the number of wells was insufficient, we took the precaution of introducing one or more common samples within each gel to standardize the results. (H) The bar graphs are the quantification of TH western blots in panel (G). (J,K) Npy and Pgc1a mRNA expression in ARH. The values are normalized to cyclophilin. Data are mean ± SEM. *P < 0.05, **P < 0.01, Two-Way ANOVA followed by Tukey post hoc. FXR-WT group is indicated as open bars, FXR-KO group as black bars. (L) Model: Hypothalamic activation of FXR decreases the activity of PKA-CREB in the hypothalamus, leading to a decrease of hypothalamic TH expression, which disrupts brain-BAT axis.