Figure 5.

Adipolin positively regulates β-hydroxybutyrate production and HMGCS2 expression in the remnant kidney after subtotal nephrectomy

(A) β-hydroxybutyrate (BHB) levels in the remnant kidney from WT and APL-KO mice at 8 weeks after subtotal nephrectomy. N = 6 in each group.

(B) BHB levels in the remnant kidney of WT mice treated with Ad-β-gal or Ad-APL at 8 weeks after subtotal nephrectomy. N = 6 in each group.

(C) mRNA levels of HMGCS2, which is a key productive enzyme of BHB, in the remnant kidney of WT and APL-KO mice at 8 weeks after subtotal nephrectomy. N = 6 in each group.

(D) mRNA levels of HMGCS2 in the remnant kidney of WT mice treated with Ad-β-gal or Ad-APL at 8 weeks after subtotal nephrectomy. N = 6 in each group.

(E) mRNA levels of HMGCS2 in HK-2 cells treated with adipolin (APL) protein (300 ng/mL) or vehicle for 6 h. N = 6 in each group.

(F) Contribution of HMGCS2 to the inhibitory effects of APL on Ang II-stimulated expression of inflammasome-related genes, including NLRP3, Caspase 1 and IL1β in HK-2 cells. HK-2 cells were treated with siRNA targeting HMGCS2 (10 nmol/L) or control unrelated siRNA for 8 h. After 16 h of serum starvation, HK-2 cells were treated with APL protein (300 ng/mL) or vehicle for 1 h followed by stimulation with Ang II (1 μmol/L) or vehicle for 24 h. N = 5 in each group. Student’s t-test (B, D and E), Wilcoxon test (A and C) and One-way ANOVA with Tukey’s multiple comparisons test (F) were used to produce the p values.