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Dietary ketone body...
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Xie, SisiFudan Univ, Peoples R China; Fujian Med Univ, Peoples R China
(författare)
Dietary ketone body-escalated histone acetylation in megakaryocytes alleviates chemotherapy-induced thrombocytopenia
- Artikel/kapitelEngelska2022
Förlag, utgivningsår, omfång ...
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AMER ASSOC ADVANCEMENT SCIENCE,2022
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:liu-191396
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-191396URI
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https://doi.org/10.1126/scitranslmed.abn9061DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:151569756URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Funding Agencies|National Key Research and Development Program, Ministry of Science and Technology of China [2021YFA0804700]; National Youth Talent Support Program (Ten Thousand Talent Program); Zhengyou Program of Fudan University; Innovation Research Team of High-level Local Universities in Shanghai; Program for Professor of Special Appointment in Shanghai (Eastern Scholar) [TP2018007]; Fujian provincial health technology project [2017-2-86]; Startup Fund For Scientific Research, Fujian Medical University [2017XQ1186]; National Natural Science Foundation of China [81600839, 82204857]; Swedish Research Council [2021-06122]; Swedish Cancer Foundation [200734PjF]
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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.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Jiang, ChenyuFudan Univ, Peoples R China
(författare)
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Wu, MengFujian Med Univ, Peoples R China
(författare)
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Ye, YingKarolinska Institutet
(författare)
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Wu, BiyingFudan Univ, Peoples R China
(författare)
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Sun, XiaotingFudan Univ, Peoples R China; Karolinska Inst, Sweden; Wenzhou Med Univ, Peoples R China
(författare)
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Lv, XueChinese Acad Med Sci & Peking Union Med Coll, Peoples R China
(författare)
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Chen, RuiboFudan Univ, Peoples R China
(författare)
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Yu, WenFudan Univ, Peoples R China
(författare)
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Sun, QiFudan Univ, Peoples R China
(författare)
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Wu, YutingFujian Med Univ, Peoples R China
(författare)
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Que, RongliangFujian Med Univ, Peoples R China
(författare)
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Li, HuilanFudan Univ, Peoples R China; Fujian Med Univ, Peoples R China
(författare)
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Yang, LingFudan Univ, Peoples R China
(författare)
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Liu, WenFudan Univ, Peoples R China
(författare)
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Zuo, JiFudan Univ, Peoples R China
(författare)
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Jensen, LasseLinköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Klinisk farmakologi(Swepub:liu)larje86
(författare)
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Huang, GuichunNanjing Univ, Peoples R China
(författare)
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Cao, YihaiKarolinska Inst, Sweden
(författare)
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Yang, YunlongFudan Univ, Peoples R China
(författare)
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Fudan Univ, Peoples R China; Fujian Med Univ, Peoples R ChinaFudan Univ, Peoples R China
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Science Translational Medicine: AMER ASSOC ADVANCEMENT SCIENCE14:6731946-62341946-6242
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Till lärosätets databas
- Av författaren/redakt...
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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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visa fler...
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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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visa färre...
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