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Dietary ketone body...
Dietary ketone body-escalated histone acetylation in megakaryocytes alleviates chemotherapy-induced thrombocytopenia
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- Xie, Sisi (author)
- Fudan Univ, Peoples R China; Fujian Med Univ, Peoples R China
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- Jiang, Chenyu (author)
- Fudan Univ, Peoples R China
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- Wu, Meng (author)
- Fujian Med Univ, Peoples R China
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- Ye, Ying (author)
- Karolinska Institutet
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- Wu, Biying (author)
- Fudan Univ, Peoples R China
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- Sun, Xiaoting (author)
- Fudan Univ, Peoples R China; Karolinska Inst, Sweden; Wenzhou Med Univ, Peoples R China
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- Lv, Xue (author)
- Chinese Acad Med Sci & Peking Union Med Coll, Peoples R China
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- Chen, Ruibo (author)
- Fudan Univ, Peoples R China
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- Yu, Wen (author)
- Fudan Univ, Peoples R China
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- Sun, Qi (author)
- Fudan Univ, Peoples R China
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- Wu, Yuting (author)
- Fujian Med Univ, Peoples R China
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- Que, Rongliang (author)
- Fujian Med Univ, Peoples R China
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- Li, Huilan (author)
- Fudan Univ, Peoples R China; Fujian Med Univ, Peoples R China
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- Yang, Ling (author)
- Fudan Univ, Peoples R China
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- Liu, Wen (author)
- Fudan Univ, Peoples R China
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- Zuo, Ji (author)
- Fudan Univ, Peoples R China
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- Jensen, Lasse (author)
- Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Klinisk farmakologi
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- Huang, Guichun (author)
- Nanjing Univ, Peoples R China
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- Cao, Yihai (author)
- Karolinska Inst, Sweden
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- Yang, Yunlong (author)
- Fudan Univ, Peoples R China
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(creator_code:org_t)
- AMER ASSOC ADVANCEMENT SCIENCE, 2022
- 2022
- English.
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In: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 14:673
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
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- Chemotherapy-induced thrombocytopenia (CIT) is a severe complication in patients with cancer that can lead to impaired therapeutic outcome and survival. Clinically, therapeutic options for CIT are limited by severe adverse effects and high economic burdens. Here, we demonstrate that ketogenic diets alleviate CIT in both animals and humans without causing thrombocytosis. Mechanistically, ketogenic diet-induced circulating beta-hydroxybutyrate (beta-OHB) increased histone H3 acetylation in bone marrow megakaryocytes. Gain- and loss-of-function experiments revealed a distinct role of 3-beta-hydroxybutyrate dehydrogenase (BDH)-mediated ketone body metabolism in promoting histone acetylation, which promoted the transcription of platelet biogenesis genes and induced thrombocytopoiesis. Genetic depletion of the megakaryocyte-specific ketone body transporter monocarboxylate transporter 1 (MCT1) or pharmacological targeting of MCT1 blocked beta-OHB-induced thrombocytopoiesis in mice. A ketogenesis-promoting diet alleviated CIT in mouse models. Moreover, a ketogenic diet modestly increased platelet counts without causing thrombocytosis in healthy volunteers, and a ketogenic lifestyle inversely correlated with CIT in patients with cancer. Together, we provide mechanistic insights into a ketone body-MCT1-BDH-histone acetylation-platelet biogenesis axis in megakaryocytes and propose a non-toxic, low-cost dietary intervention for combating CIT.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Annan klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Other Clinical Medicine (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Xie, Sisi
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Jiang, Chenyu
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Wu, Meng
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Ye, Ying
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Wu, Biying
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Sun, Xiaoting
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show more...
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Lv, Xue
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Chen, Ruibo
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Yu, Wen
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Sun, Qi
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Wu, Yuting
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Que, Rongliang
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Li, Huilan
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Yang, Ling
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Liu, Wen
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Zuo, Ji
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Jensen, Lasse
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Huang, Guichun
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Cao, Yihai
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Yang, Yunlong
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Other Clinical M ...
- Articles in the publication
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Science Translat ...
- By the university
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Linköping University
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Karolinska Institutet