Ketone body oxidation increases cardiac endothelial cell proliferation.
angiogenesis
endothelial cell
heart
ketogenic diet
ketone bodies
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
07 04 2022
07 04 2022
Historique:
revised:
20
01
2022
received:
21
06
2021
accepted:
24
01
2022
pubmed:
19
2
2022
medline:
9
4
2022
entrez:
18
2
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35179309
doi: 10.15252/emmm.202114753
pmc: PMC8988203
doi:
Substances chimiques
Ketone Bodies
0
Glucose
IY9XDZ35W2
Banques de données
GEO
['GSE191173']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14753Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK091538
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.
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