Fig. 5. In vivo knockdown of LXR and PPARγ normalizes liver steatosis in HMGB1^ΔHep mice.

(A and B) HMGB1^fl/fl [vehicle (Veh), n = 5; T0901317 (T09), n = 10] and HMGB1^ΔHep (Veh, n = 3; T09, n = 7) mice were treated with either vehicle (5% carboxymethylcellulose) or LXR synthetic agonist T0901317 (oral gavage, 30 mg/kg per day) for four consecutive days. After 6-hour starvation on the last day, mice were sacrificed. (A) Liver tissue was then subjected to RT-qPCR analysis of the indicated LXR-dependent genes. (B) HMGB1^fl/fl (n = 10) and HMGB1^ΔHep (n = 12) mice were infected with either adenovirus expressing an LXR shRNA or a scramble (SCR) sequence and then subjected 7 days later to an F/R challenge. Liver steatosis was determined by Oil Red O (ORO) staining on liver sections, with the quantitative representation displayed on the right. (C) HMGB1^fl/fl [Veh, n = 4 to 6; rosiglitazone (Rosi), n = 7] and HMGB1^ΔHep (Veh, n = 4 to 6; Rosi, n = 8) mice were treated with either vehicle [5% dimethyl sulfoxide (DMSO) in saline] or PPARγ synthetic agonist rosiglitazone (30 mg/kg per day, intravenously) and were sacrificed 18 hours later. Liver tissue was then subjected to RT-qPCR analysis of the indicated PPARγ-dependent genes. (D) HMGB1^fl/fl (ShSCR, n = 7; ShPPARγ, n = 8) and HMGB1^ΔHep (ShSCR, n = 8; ShPPARγ, n = 7) mice were infected with either adenovirus expressing a PPARγ shRNA or a scramble (SCR) sequence and then subjected 7 days later to an F/R challenge. Liver steatosis was determined by Oil Red O staining on liver sections. Data are means ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001, HMGB1^fl/fl and HMGB1^ΔHep comparison, by unpaired Mann-Whitney comparison. ^$P < 0.05 and ^$$P < 0.01, for treatment effect by one-way ANOVA.