Fig. 7

BDH1 represses LCN2 expression via inhibiting H3K9 β-hydroxybutyrylation. A, B ELISA analysis showing the concentrations of βOHB and AcAc in cardiac tissues from db/m or db/db mice. C–F ELISA analysis showing the concentrations of βOHB and AcAc in cardiac tissues from db/m or db/db mice injected with AAV9-Con or AAV9-Bdh1 (C, D) and cardiac tissues from db/m; WT, db/m; Bdh1−/−, db/db; WT and db/db; Bdh1−/− mice (E, F). G, H ELISA analysis showing the concentrations of βOHB and AcAc in Vehicle- or PA-treated H9C2 cells. I–L ELISA analysis showing the concentrations of βOHB and AcAc in Vector- or Flag-BDH1-transfected H9C2 cells with or without PA treatment (I, J) and H9C2 cells transfected with siNC or siBdh1 (K, L). M, N Western blot analysis showing the H3K9 β-hydroxybutyrylation (M) and acetylation (N) levels in Vehicle- or PA-treated H9C2 cells transfected with Vector- or Flag-BDH1. O,P Western blot analysis showing the H3K9 β-hydroxybutyrylation and acetylation levels in PA-treated H9C2 cells transfected with siNC- or siBdh1 (O) and cardiac tissues from db/m or db/db mice injected with AAV9-Con or AAV9-Bdh1 (P). Q Illustration showing the localization of primers on the Lcn2 promoter. R, S ChIP assay showing the H3K9bhb enrichment on the Lcn2 promoter in the PA-treated H9C2 cells transfected with siNC or siBdh1 (R) and Vector- or Flag-BDH1-transfected H9C2 cells with or without PA treatment (S). T Illustration showing the BDH1 overexpression-mediated βOHB reduction and the following decreased H3K9bhb on the Lcn2 promoter. n = 6 mice per group in A–C. All results are representative of three independent experiments. Values are presented as mean ± SD. *p < 0.05; **p < 0.01; ***p < 0.001