Figure 7. Intestinal FXR mediates changes in lipid absorption, whereas hepatic FXR controls lipid synthesis.

(A, C, and E) Experiment schematics: wild-type or (A) Shp^−/− mice, (C) Srebp1c^−/− mice, or (E) Fxr^fl/fl, Fxr^Liv-KO, and Fxr^Int-KO mice were fed a Western diet for 8 weeks and treated with either vehicle or GSK2324.

(B and D) Lipidomic analysis of hepatic lipid classes in WD-fed (B) Shp^−/− mice and (D) Srebp1c^−/− mice.

(F) Hepatic mRNA expression of FXR target gene Shp in mice from (E).

(G) Ileal mRNA expression of FXR target gene FGF15 in mice from (E).

(H) Lipidomic analysis of hepatic lipid classes in mice from (E).

(I) Hepatic mRNA expression of select lipogenic genes in mice from (E).

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

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

Data are represented as mean ± SEM with individual animals noted as dots. *p < 0.05, **p < 0.01, ***p < 0.001. See also Figure S7.