Triheptanoin partially restores levels of tricarboxylic acid cycle intermediates in the mouse pilocarpine model of epilepsy

J Neurochem. 2014 Apr;129(1):107-19. doi: 10.1111/jnc.12610. Epub 2013 Dec 2.


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.

Keywords: 13C isotope; NMR spectroscopy; anaplerosis; medium chain triglyceride; seizures; status epilepticus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Citric Acid Cycle / drug effects
  • Citric Acid Cycle / physiology*
  • Disease Models, Animal*
  • Epilepsy / chemically induced
  • Epilepsy / drug therapy
  • Epilepsy / metabolism*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Mice
  • Pilocarpine / toxicity*
  • Random Allocation
  • Triglycerides / administration & dosage*


  • Triglycerides
  • Pilocarpine
  • triheptanoin