Figure 5. Inhibition of xCT mitigates alcoholic steatosis.

(A) Schematic for the experimental protocol. WT C57BL/6J mice were injected with AAV-Slc7a11-shRNA (2 × 10¹¹ vg/mouse) or control and, two weeks later, fed with ethanol diet for 8 weeks (n = 5/group; 2 replicates). Western blot analysis for hepatic xCT at sacrifice.

(B) Schematic for the experimental protocol. Body weight changes of WT C57BL/6J mice treated with vehicle or sulfasalazine (SSZ; 100 mg kg⁻¹ body weight, i.p., every day) for the last four weeks of ethanol feeding (n = 4/group; 2 replicates).

(C-E) Serum levels of ALT (C), glutamate (D), and hepatic concentration of 2-AG (E) in shRNA- or SSZ-treated mice with their corresponding controls after chronic ethanol feeding.

(F) Representative Oil Red O stainings on the liver tissue sections of shRNA- or SSZ-treated mice with their corresponding controls.

(G) qRT-PCR assays for Cnr1, Srebf1, and Fasn in each group (n = 4/group).

(H) Hepatocyte-specific xCT KO (AlbCre) mice were obtained by crossing xCT^flox/flox mice with Alb^cre mice. Western blot analysis for hepatic xCT in WT and AlbCre mice.

(I) Serum levels of ALT in WT and AlbCre mice after ethanol diet feeding for 8 weeks (n = 4/group; 2 replicates).

(J) Representative H&E and Oil Red O stainings on the liver tissue sections of WT and AlbCre mice with their corresponding controls.

(K) qRT-PCR assays for Cnr1, Srebf1, Fasn, Cat, Sod1 and Sod2 in each group (n = 4/group).

Data are presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001. Scale bars, 50 μm.

See also Figure S4.