DCA relieved hepatomegaly and reduced liver lipid droplet accumulation in FXR-null mice. Mice were divided into WT mice-saline group, FXR-null mice-saline group, FXR-null mice-100 mg/kg/day (low) DCA group, FXR-null mice-300 mg/kg/day (high) DCA group. All the mice were fed a high-fat diet for two months. (a) Experimental protocol of the in vivo study. (b, c) DCA alleviated glucose tolerance in FXR-null mice. After 49 days, the mice were subjected to a glucose tolerance test, n = 10. (d, e) DCA enhanced insulin sensitivity in FXR-null mice. After the 54th day, the mice were subjected to an insulin sensitivity test. n = 10. (f–h) DCA reduced blood lipids in FXR-null mice. NEFA, TC, and TG content in FXR-null mice with DCA treatment, n = 10. (i, j) DCA treatment reduced hepatic TG and FFA level, n = 10. (k) DCA reduced hepatocytes lipid deposition. PV: portal vein. Upper panel: bar, 200 μm, representative images H&E staining of liver tissues; middle panel: bar, 200 μm, lower panel: bar, 50 μm; both of them representative images of Oil Red O staining of liver tissues; WT: n = 3, KO: n = 3. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001, ∗∗∗∗P < 0.0001.