Research Paper Volume 15, Issue 22 pp 13384—13410

BDH1-mediated βOHB metabolism ameliorates diabetic kidney disease by activation of NRF2-mediated antioxidative pathway

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Figure 8. Ketogenic diet alleviates the progression of DKD. (A) Schematic diagram illustrating the animal experimental design. During the experiment, m/m mice were fed with CD, while db/db mice were fed with SD or KD starting at eight-week-old. Mice were euthanized at nine weeks after KD intervention. A schematic representation of the KD intervention strategy in db/db mice. (B) Blood level of βOHB in mice from indicated groups (n = 5 in m/m group; n = 4 in SD and KD groups). (C) Urinary ACR values of mice in indicated groups (n = 5 in m/m group; n = 4 in SD and KD groups). (D) Representative WB image showing the protein level of BDH1 in the kidneys of indicated groups. (E) Representative photomicrographs of H&E, Masson, IHC (IL-1β), and TUNEL staining showing the pathological changes in the kidneys of indicated groups. (F) Quantification of the fibrosis area in the kidneys of indicated groups (n = 4 per group). (G) Quantification of apoptosis-positive cells in the kidneys of indicated groups (n = 4 per group). All results are representative of three independent experiments. Values are presented as mean ± standard deviation. Bar: 100 μm in E. Abbreviations: ACR: albumin-to-creatinine ratio; SD: standard diet; KD: ketogenic diet; DKD: diabetic kidney disease; BDH1: β-hydroxybutyrate dehydrogenase 1; βOHB: β-hydroxybutyrate; WB: western blot; H&E: hematoxylin and eosin; IHC: immunohistochemistry. *P < 0.05; **P < 0.01; ***P < 0.001. Abbreviation: ns: no significance.