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-(13) C]
glucose 3.5-4 weeks after
pilocarpine-induced
status epilepticus (SE) fed either a control or
triheptanoin diet. Amounts of metabolites and incorporations of (13) C were determined in extracts of cerebral cortices and hippocampal formation and
enzyme activity and
mRNA expression were quantified. The percentage enrichment with two (13) C 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 (13) C labeling. Reduced
pyruvate carboxylase mRNA and
enzyme activity in forebrains and decreased [2,3-(13) C]
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.