Fig. 5.

The miR-22 inhibitor enhances the effect of OCA in reducing steatosis, improving insulin sensitivity, and inducing FGF21 signaling.

C57BL/6 male mice were fed a WD after weaning. When those mice were 7 months old, they received OCA (10 μg/g body weight, daily oral gavage), adenovirus negative control, or the miR-22 inhibitor (1×10⁹ PFU, tail vein injection, once a week), or a combination of OCA plus the miR-22 inhibitor for 3 weeks. Age- and sex-matched CD-fed mice without any treatment were used as baseline controls. The same diet was given during the interventions. (A) Representative gross liver morphology and H&E-stained liver sections; (B) steatosis scores; (C) glycemic response measured by ITT; (D) serum GLP-1 secretion; (E) serum FGF21 level; (F) hepatic cholesterol and triglyceride levels; Hepatic fat content was scored as 0 (<5%), 1 (5–33%), 2 (34–66%), and 3 (>67%). Data are shown as mean ± SD (n = 4). One-way ANOVA with Tukey’s t-test. ^#p <0.05, ^##p <0.01, ^###p <0.001 between WD and CD; ∗p <0.05, ∗∗p <0.01, ∗∗∗p <0.0001 between treated groups and controls; ^$p <0.05, ^$$$p <0.001 between combination and single treatment. CD, control diet; ITT, insulin tolerance test; OCA, obeticholic acid; PFUs, plaque-forming units; WD, Western diet.