Figure 6. In an NAFLD model, FXR activation dramatically decreases hepatic TAG and intestinal lipid absorption.

(A) Experiment schematic of diet-induced NAFLD model. Wild-type or Fxr^−/− mice fed WD for 8 weeks were treated for 3 days with vehicle or FXR agonist GSK2324 (n = 8–10/group).

(B) Hepatic mRNA expression of FXR target genes Shp and MafG in mice from (A).

(C and D) Lipidomic analyses of (C) hepatic lipid classes (nmol/mg liver) and (D) hepatic TAG species (nmol/mg liver) in mice from (A).

(E) Total bile acid pool amount from mice in (A).

(F and J) Experiment schematic for absorption methods. WD-fed wild-type mice were treated with either vehicle or GSK2324 and (F) gavaged with ¹⁴C triolein or with fatty acid conjugated to BODIPY fluorophore, or (J) fed a diet containing non-absorbable lipid standard sucrose polybehenate (C22:0, n = 10/group).

(G and H) Representative images (G) and fluorescence quantification (H) from intestinal sections of BODIPY-gavaged mice treated as in (F).

(I) Liver radioactive counts from ¹⁴C triolein-gavaged mice as in (F).

(K) Fecal fatty acids after treatment with either vehicle or GSK2324 in mice as in (J).

Data are represented as mean ± SEM with individual animals noted as dots. **p < 0.01, ***p < 0.001. See also Figure S6.