A novel hepatocyte ketone production assay to help the selection of nutrients for the ketogenic diet treatment of epilepsy.
Dietary fat
In vitro assay
Ketogenic diet
Lipids/oxidation
Liver
Nutrition
Omega-3 fatty acids
β-Hydroxybutyrate
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
24 May 2024
24 May 2024
Historique:
received:
15
08
2023
accepted:
21
05
2024
medline:
25
5
2024
pubmed:
25
5
2024
entrez:
24
5
2024
Statut:
epublish
Résumé
The classic ketogenic diet is an effective treatment option for drug-resistant epilepsy, but its high fat content challenges patient compliance. Optimizing liver ketone production guided by a method comparing substrates for their ketogenic potential may help to reduce the fat content of the diet without loss in ketosis induction. Here, we present a liver cell assay measuring the β-hydroxybutyrate (βHB) yield from fatty acid substrates. Even chain albumin-conjugated fatty acids comprising between 4 and 18 carbon atoms showed a sigmoidal concentration-βHB response curve (CRC) whereas acetate and omega-3 PUFAs produced no CRC. While CRCs were not distinguished by their half-maximal effective concentration (EC50), they differed by maximum response, which related inversely to the carbon chain length and was highest for butyrate. The assay also suitably assessed the βHB yield from fatty acid blends detecting shifts in maximum response from exchanging medium chain fatty acids for long chain fatty acids. The assay further detected a dual role for butyrate and hexanoic acid as ketogenic substrate at high concentration and ketogenic enhancer at low concentration, augmenting the βHB yield from oleic acid and a fatty acid blend. The assay also found propionate to inhibit ketogenesis from oleic acid and a fatty acid blend at low physiological concentration. Although the in vitro assay shows promise as a tool to optimize the ketogenic yield of a fat blend, its predictive value requires human validation.
Identifiants
pubmed: 38789658
doi: 10.1038/s41598-024-62723-7
pii: 10.1038/s41598-024-62723-7
doi:
Substances chimiques
Ketones
0
3-Hydroxybutyric Acid
TZP1275679
Fatty Acids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
11940Subventions
Organisme : Netherlands Organization for Scientific Research
ID : NWA.ID.17.161
Informations de copyright
© 2024. The Author(s).
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