Ketone body oxidation increases cardiac endothelial cell proliferation
Abstract Blood vessel formation is dependent on metabolic adaption in endothelial cells. Glucose and fatty acids are essential substrates for ATP and biomass production; however, the metabolism of other substrates remains poorly understood. Ketone bodies are important nutrients for cardiomyocytes du...
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| Format: | Article |
| Language: | English |
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Springer Nature
2022-02-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202114753 |
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| author | Eva‐Maria Weis Patrycja Puchalska Alisa B Nelson Jacqueline Taylor Iris Moll Sana S Hasan Matthias Dewenter Marco Hagenmüller Thomas Fleming Gernot Poschet Agnes Hotz‐Wagenblatt Johannes Backs Peter A Crawford Andreas Fischer |
| author_facet | Eva‐Maria Weis Patrycja Puchalska Alisa B Nelson Jacqueline Taylor Iris Moll Sana S Hasan Matthias Dewenter Marco Hagenmüller Thomas Fleming Gernot Poschet Agnes Hotz‐Wagenblatt Johannes Backs Peter A Crawford Andreas Fischer |
| author_sort | Eva‐Maria Weis |
| collection | DOAJ |
| description | Abstract Blood vessel formation is dependent on metabolic adaption in endothelial cells. Glucose and fatty acids are essential substrates for ATP and biomass production; however, the metabolism of other substrates remains poorly understood. Ketone bodies are important nutrients for cardiomyocytes during starvation or consumption of carbohydrate‐restrictive diets. This raises the question whether cardiac endothelial cells would not only transport ketone bodies but also consume some of these to achieve their metabolic needs. Here, we report that cardiac endothelial cells are able to oxidize ketone bodies and that this enhances cell proliferation, migration, and vessel sprouting. Mechanistically, this requires succinyl‐CoA:3‐oxoacid‐CoA transferase, a key enzyme of ketone body oxidation. Targeted metabolite profiling revealed that carbon from ketone bodies got incorporated into tricarboxylic acid cycle intermediates as well as other metabolites fueling biomass production. Elevation of ketone body levels by a high‐fat, low‐carbohydrate ketogenic diet transiently increased endothelial cell proliferation in mouse hearts. Notably, in a mouse model of heart hypertrophy, ketogenic diet prevented blood vessel rarefication. This suggests a potential beneficial role of dietary intervention in heart diseases. |
| format | Article |
| id | doaj-art-ef5eaa2a664147ecb470d7766f67d5df |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2022-02-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-ef5eaa2a664147ecb470d7766f67d5df2025-08-20T03:46:13ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842022-02-0114411810.15252/emmm.202114753Ketone body oxidation increases cardiac endothelial cell proliferationEva‐Maria Weis0Patrycja Puchalska1Alisa B Nelson2Jacqueline Taylor3Iris Moll4Sana S Hasan5Matthias Dewenter6Marco Hagenmüller7Thomas Fleming8Gernot Poschet9Agnes Hotz‐Wagenblatt10Johannes Backs11Peter A Crawford12Andreas Fischer13Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ)Division of Molecular Medicine, Department of Medicine, University of MinnesotaDivision of Molecular Medicine, Department of Medicine, University of MinnesotaDivision Vascular Signaling and Cancer, German Cancer Research Center (DKFZ)Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ)Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ)Institute of Experimental Cardiology, Heidelberg University HospitalInstitute of Experimental Cardiology, Heidelberg University HospitalDepartment of Internal Medicine I and Clinical Chemistry, University Hospital HeidelbergCentre for Organismal Studies (COS), Heidelberg UniversityCore Facility Omics IT and Data Management (ODCF), German Cancer Research Center (DKFZ)Institute of Experimental Cardiology, Heidelberg University HospitalDivision of Molecular Medicine, Department of Medicine, University of MinnesotaDivision Vascular Signaling and Cancer, German Cancer Research Center (DKFZ)Abstract Blood vessel formation is dependent on metabolic adaption in endothelial cells. Glucose and fatty acids are essential substrates for ATP and biomass production; however, the metabolism of other substrates remains poorly understood. Ketone bodies are important nutrients for cardiomyocytes during starvation or consumption of carbohydrate‐restrictive diets. This raises the question whether cardiac endothelial cells would not only transport ketone bodies but also consume some of these to achieve their metabolic needs. Here, we report that cardiac endothelial cells are able to oxidize ketone bodies and that this enhances cell proliferation, migration, and vessel sprouting. Mechanistically, this requires succinyl‐CoA:3‐oxoacid‐CoA transferase, a key enzyme of ketone body oxidation. Targeted metabolite profiling revealed that carbon from ketone bodies got incorporated into tricarboxylic acid cycle intermediates as well as other metabolites fueling biomass production. Elevation of ketone body levels by a high‐fat, low‐carbohydrate ketogenic diet transiently increased endothelial cell proliferation in mouse hearts. Notably, in a mouse model of heart hypertrophy, ketogenic diet prevented blood vessel rarefication. This suggests a potential beneficial role of dietary intervention in heart diseases.https://doi.org/10.15252/emmm.202114753angiogenesisendothelial cellheartketogenic dietketone bodies |
| spellingShingle | Eva‐Maria Weis Patrycja Puchalska Alisa B Nelson Jacqueline Taylor Iris Moll Sana S Hasan Matthias Dewenter Marco Hagenmüller Thomas Fleming Gernot Poschet Agnes Hotz‐Wagenblatt Johannes Backs Peter A Crawford Andreas Fischer Ketone body oxidation increases cardiac endothelial cell proliferation EMBO Molecular Medicine angiogenesis endothelial cell heart ketogenic diet ketone bodies |
| title | Ketone body oxidation increases cardiac endothelial cell proliferation |
| title_full | Ketone body oxidation increases cardiac endothelial cell proliferation |
| title_fullStr | Ketone body oxidation increases cardiac endothelial cell proliferation |
| title_full_unstemmed | Ketone body oxidation increases cardiac endothelial cell proliferation |
| title_short | Ketone body oxidation increases cardiac endothelial cell proliferation |
| title_sort | ketone body oxidation increases cardiac endothelial cell proliferation |
| topic | angiogenesis endothelial cell heart ketogenic diet ketone bodies |
| url | https://doi.org/10.15252/emmm.202114753 |
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