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Triheptanoin--a medium chain triglyceride with odd chain fatty acids: a new anaplerotic anticonvulsant treatment?

Abstract
The triglyceride of heptanoate (C7 fatty acid), triheptanoin, is a tasteless oil used to treat rare metabolic disorders in USA and France. Heptanoate is metabolized by β-oxidation to provide propionyl-CoA, which after carboxylation can produce succinyl-CoA, resulting in anaplerosis - the refilling of the tricarboxylic acid cycle. Heptanoate is also metabolized by the liver to the C5 ketones, β-ketopentanoate and/or β-hydroxypentanoate, which are released into the blood and thought to enter the brain via monocarboxylate transporters. Oral triheptanoin has recently been discovered to be reproducibly anticonvulsant in acute and chronic mouse seizures models. However, current knowledge on alterations of brain metabolism after triheptanoin administration and anaplerosis via propionyl-CoA carboxylation in the brain is limited. This review outlines triheptanoin's unique anticonvulsant profile and its clinical potential for the treatment of medically refractory epilepsy. Anaplerosis as a therapeutic approach for the treatment of epilepsy is discussed. More research is needed to elucidate the anticonvulsant mechanism of triheptanoin and to reveal its clinical potential for the treatment of epilepsy and other disorders of the brain.
AuthorsKarin Borges, Ursula Sonnewald
JournalEpilepsy research (Epilepsy Res) Vol. 100 Issue 3 Pg. 239-44 (Jul 2012) ISSN: 1872-6844 [Electronic] Netherlands
PMID21855298 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
CopyrightCopyright © 2011 Elsevier B.V. All rights reserved.
Chemical References
  • Acyl Coenzyme A
  • Anticonvulsants
  • Fatty Acids
  • Triglycerides
  • triheptanoin
  • propionyl-coenzyme A
Topics
  • Acyl Coenzyme A (metabolism)
  • Animals
  • Anticonvulsants (metabolism, therapeutic use)
  • Epilepsy (drug therapy, metabolism)
  • Fatty Acids (metabolism)
  • Humans
  • Triglycerides (metabolism, therapeutic use)

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