Research Paper Volume 15, Issue 22 pp 13384—13410

Figure 5. BDH1-mediated βOHB metabolism promotes fumarate production through the AcAc–succinate–fumarate metabolic pathway. (A) Concentrations of AcAc, succinate, and fumarate in HK-2 cells transfected with NC siRNA or Bdh1 siRNA. (B, C) Concentrations of AcAc, succinate, and fumarate in BDH1-overexpressed HK-2 cells stimulated with HG (B) or PA (C). (D, E) Concentrations of AcAc, succinate, and fumarate in βOHB-supplemented HK-2 cells stimulated with HG (D) or PA (E). (F) Concentrations of βOHB, AcAc, succinate, and fumarate in the kidneys of indicated groups (n = 5 in m/m group, n = 4 in vector, and AAV-Bdh1-GFP injected db/db group). (G) Scheme showing the BDH1-regulated metabolic flux composed of βOHB–AcAc–succinate–fumarate. All results are representative of three independent experiments. Values are presented as mean ± standard deviation. Abbreviations: BDH1: β-hydroxybutyrate dehydrogenase 1; βOHB: β-hydroxybutyrate; AcAc: acetoacetate; TCA: tricarboxylic acid; HG: high glucose; PA: palmitic acid; βOHB: β-hydroxybutyrate; AcAc: acetoacetate. ^*P < 0.05; ^**P < 0.01; ^***P < 0.001.