High fat ketogenic diet envisioned as potential life-saving therapy to combat low platelets in cancer patients


Ketogenic diet promotes megakaryopoiesis and platelet production via β-OHB (A) ELISA detection of serum TPO, c-Mpl, and IL-6 concentrations in control or KDtreated mice at day 7 (n = 6 samples per group). (B) Representative immunofluorescence micrograph of isolated primary MKs stained with CD41 (red) and DAPI (blue). Scale bar: 20 μm. Quantification of CD41+ cells in isolated cells (n = 8 random fields per group). (C) Representative transmission electron microscopy micrographs of isolated primary MKs from control or KD-treated mice. Red arrowhead: nucleus. Yellow arrowhead: pre-DMS. Blue arrowhead: cytoplasmic rearrangements. Scale bar in upper panel: 2 μm. Scale bar in middle panel: 500 nm. Scale bar in lower panel: 1 μm. (D) Quantification of cell viability in vehicle- or β-OHB-treated MKs (n = 5 samples per group). QPCR detection of Nfe2 and Gata1 RNA expressions in MK treated with various doses of β-OHB (n = 3 samples per group). (E) QPCR quantification of Bdh1 and Bdh2 mRNA expression in MK transfected with scramble siRNA or Bdh1/2 siRNA (n = 3 samples per group). (F) Phalloidin (green) and DAPI (blue) immunofluorescent staining micrographs of human MEG-01 cells treated with vehicle or 2 mM β-OHB. Scale bar: 150 μm. Quantifications of MK number per field (n = 8 random fields per group). (G) Representative transmission electron microscopy micrographs of human MEG-01 cells treated with vehicle or 2 mM β-OHB. Red arrowhead: nucleus. Yellow arrowhead: pre-DMS. Blue arrowhead: cytoplasmic rearrangements. Scale bar in upper panel: 2 μm. Scale bar in middle panel: 500 nm. Scale bar in lower panel: 1 μm. (H) Megakaryopoiesis- and thrombocytopoiesisassociated gene expression of human MEG-01 cells form vehicle- or β-OHB-stimulated MKs pre-treated with or without MCT1 inhibitor AZD3965 (n = 3 samples per group). (I) Megakaryopoiesis- and thrombocytopoiesis-associated gene expression of vehicle- or β-OHB-stimulated human MEG-01 cells pre-treated with or without BDH1/2 siRNA (n = 3 samples per group). *pScience Translational Medicine (2022). DOI: 10.1126/scitranslmed.abn9061

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