Journal
JOURNAL OF NEUROCHEMISTRY
Volume 129, Issue 1, Pages 107-119Publisher
WILEY-BLACKWELL
DOI: 10.1111/jnc.12610
Keywords
anaplerosis; NMR spectroscopy; status epilepticus; C-13 isotope; seizures; medium chain triglyceride
Categories
Funding
- Australian National Health and Research Council [63145, 1044407]
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Triheptanoin, the triglyceride of heptanoate, is anticonvulsant in various epilepsy models. It is thought to improve energy metabolism in the epileptic brain by re-filling the tricarboxylic acid (TCA) cycle with C4-intermediates (anaplerosis). Here, we injected mice with [1,2-C-13]glucose 3.5-4weeks after pilocarpine-induced status epilepticus (SE) fed either a control or triheptanoin diet. Amounts of metabolites and incorporations of C-13 were determined in extracts of cerebral cortices and hippocampal formation and enzyme activity and mRNA expression were quantified. The percentage enrichment with two C-13 atoms in malate, citrate, succinate, and GABA was reduced in hippocampal formation of control-fed SE compared with control mice. Except for succinate, these reductions were not found in triheptanoin-fed SE mice, indicating that triheptanoin prevented a decrease of TCA cycle capacity. Compared to those on control diet, triheptanoin-fed SE mice showed few changes in most other metabolite levels and their C-13 labeling. Reduced pyruvate carboxylase mRNA and enzyme activity in forebrains and decreased [2,3-C-13]aspartate amounts in cortex suggest a pyruvate carboxylation independent source of C-4 TCA cycle intermediates. Most likely anaplerosis was kept unchanged by carboxylation of propionyl-CoA derived from heptanoate. Further studies are proposed to fully understand triheptanoin's effects on neuroglial metabolism and interaction.
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