β-Hydroxybutyrate and Medium-Chain Fatty Acids are Metabolized by Different Cell Types in Mouse Cerebral Cortex Slices

Research output: Contribution to journalComment/debatepeer-review

Ketogenic diets and medium-chain triglycerides are gaining attention as treatment of neurological disorders. Their major metabolites, beta-hydroxybutyrate (beta HB) and the medium-chain fatty acids (MCFAs) octanoic acid (C8) and decanoic acid (C10), are auxiliary brain fuels. To which extent these fuels compete for metabolism in different brain cell types is unknown. Here, we used acutely isolated mouse cerebral cortical slices to (1) compare metabolism of 200 mu M [U-C-13]C8, [U-C-13]C10 and [U-C-13]beta HB and (2) assess potential competition between metabolism of beta HB and MCFAs by quantifying metabolite C-13 enrichment using gas chromatography-mass spectrometry (GC-MS) analysis. The C-13 enrichment in most metabolites was similar with [U-C-13]C8 and [U-C-13]C10 as substrates, but several fold lower with [U-C-13]beta HB. The C-13 enrichment in glutamate was in a similar range for all three substrates, whereas the C-13 enrichments in citrate and glutamine were markedly higher with both [U-C-13]C8 and [U-C-13]C10 compared with [U-C-13]beta HB. As citrate and glutamine are indicators of astrocytic metabolism, the results indicate active MCFA metabolism in astrocytes, while beta HB is metabolized in a different cellular compartment. In competition experiments, C-12-beta HB altered C-13 incorporation from [U-C-13]C8 and [U-C-13]C10 in only a few instances, while C-12-C8 and C-12-C10 only further decreased the low [U-C-13]beta HB-derived C-13 incorporation into citrate and glutamine, signifying little competition for oxidative metabolism between beta HB and the MCFAs. Overall, the data demonstrate that beta HB and MCFAs are supplementary fuels in different cellular compartments in the brain without notable competition. Thus, the use of medium-chain triglycerides in ketogenic diets is likely to be beneficial in conditions with carbon and energy shortages in both astrocytes and neurons, such as GLUT1 deficiency.

Original languageEnglish
JournalNeurochemical Research
Volume48
Pages (from-to)54–61
ISSN0364-3190
DOIs
Publication statusPublished - 2023

    Research areas

  • Astrocytes, MCFA, Ketone bodies, Octanoic acid, Decanoic acid, Epilepsy

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